Datasets:

hippocrates

/

CitationGPTv2_test

like 0

CitationGPTRetr600

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron Pathophysiology in Alzheimer's Diseases. Abstract of the paper: Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Increasing evidence suggests that disorders of metal ion metabolism in the brain are one of the risk factors for the pathogenesis of AD. Iron, one of the endogenous metal ions, involves in many important physiological activities in the brain. Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, lactoferrin. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, leads to cell death, and ultimately influences the process of β-amyloid (Aβ) misfolding and plaque aggregation. Although the results are different, in general, iron has deposition in different brain regions of AD patients, which may impair normal cognitive function and behavior. Therefore, neuroimaging changes have so far been largely attributed to focal iron deposition accompanying the plaques at preclinical stages of AD, and iron-targeted therapeutic strategies have become a new direction. Iron chelators have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Future research will also focus on iron as an opportunity to study the mechanism of the occurrence and development of AD from the iron steady state to more fully clarify the etiology and prevention strategies.

False

CitationGPTRetr601

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron and Alzheimer's Disease: An Update on Emerging Mechanisms. Abstract of the paper: Iron is a crucial transition metal for life and is the most abundant transition metal in the brain. However, iron's biological utility as an effective redox cycling metal also endows it with the potential to catalyze production of noxious free radicals. This "Janus-faced" nature of iron demands a tight regulation of cellular its metabolism. This regulation is crucial in the CNS, where iron plays myriad keystone roles in CNS processes, including mitochondrial energy transduction, enzyme catalysis, mitochondrial function, myelination, neurotransmitter anabolism and catabolism. Aberrations in brain iron homeostasis can elevate levels of this redox-active metal, leading to mislocalization of the metal and catastrophic oxidative damage to sensitive cellular and subcellular structures. Iron dyshomeostasis has been strongly linked to the pathogenesis of Alzheimer's disease (AD), as well as other major neurodegenerative diseases. Despite the growing societal burden of AD, no disease-modifying therapy exists, necessitating continued investment into both drug-development and the fundamental science investigating the disease-causing mechanisms. Targeting iron dyshomeostasis in the brain represents a rational approach to treat the underlying disease. Here we provide an update on known and emerging iron-associated mechanisms involved in AD. We conclude with an overview of evidence suggesting that, in addition to apoptosis, neuronal loss in AD involves "ferroptosis", a newly discovered iron- and lipid-peroxidation-dependent form of regulated necrosis. The ferroptosis field is rapidly progressing and may provide key insights for future drug-development with disease-modifying potential in AD.

False

CitationGPTRetr602

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology. Abstract of the paper: Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (β [SE] = 9.7 [2.6]; P = 3.0 × 10-4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: β [SE] = -0.040 [0.005], P = 1.6 × 10-14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.

True

CitationGPTRetr603

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Cobalamin levels are not reduced in Alzheimer's disease: results from a population-based study. Abstract of the paper: OBJECTIVE To determine whether there is a relationship between serum cobalamin levels, normal aging, and Alzheimer's Disease (AD). DESIGN Cross-sectional survey. SETTING A district (Kungsholmen) in Stockholm, Sweden. PARTICIPANTS Population-based cohort of 545 subjects aged more than 74 years. The sample was selected on the basis of evidence of cognitive impairment from all inhabitants in an area of Stockholm (2368 individuals), both living at home or in institutions. MEASUREMENTS Serum cobalamin levels and diagnostic evaluation for a diagnosis of dementia and type of dementia. RESULTS The serum cobalamin levels in non-demented individuals decreased 5.5 pmol/L with an increase of 1 year of age (regression coefficient = -5.53; P < 0.0001). However, the regression coefficient was 0.21 (P = 0.91) in demented people and 2.57 (P = 0.32) in AD subjects. There was no difference between serum cobalamin levels in demented, AD, and non-demented subjects, except for the oldest ages where demented people and AD sufferers showed higher values. AD patients still living in their own homes had significantly lower cobalamin concentrations compared with institutionalized AD sufferers. The prevalence rate of cobalamin deficiency was 15.5% (95% CI = 11.5-19.5) in normal aging and 18.1% (95% CI = 10.3-25.9) in AD. CONCLUSIONS These data suggest that serum cobalamin levels decrease in normal aging, but not in dementia or AD. A lower cobalamin concentration observed in AD sufferers still living in their own homes compared with institutionalized persons with AD seemed to be related to but not fully explained by eating habits. Patients with AD living in their own homes are at risk of developing cobalamin deficiency, and monitoring of serum cobalamin concentrations might be useful in this group.

False

CitationGPTRetr604

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Cerebrospinal fluid levels of transition metals in patients with Alzheimer's disease. Abstract of the paper: We compared CSF and serum levels of iron, copper, manganese, and zinc, measured by atomic absorption spectrophotometry, in 26 patients patients with Alzheimer's disease (AD) without major clinical signs of undernutrition, and 28 matched controls. CSF zinc levels were significantly decreased in AD patients as compared with controls (p < 0.05). The serum levels of zinc, and the CSF and serum levels of iron, copper, and manganese, did not differ significantly between AD-patient and control groups. These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. Weight and body mass index were significantly lower in AD patients than in controls. Because serum zinc levels were normal, the possibility that low CSF zinc levels were due to a deficiency of dietary intake seems unlikely. However, it is possible that they might be related to the interaction of beta-amyloid and/or amyloid precursor protein with zinc, that could result in a depletion of zinc levels.

False

CitationGPTRetr605

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. Abstract of the paper: It is now established that oxidative stress is one of the earliest, if not the earliest, change that occurs in the pathogenesis of Alzheimer's disease (AD). Consistent with this, mild cognitive impairment (MCI), the clinical precursor of AD, is also characterized by elevations in oxidative stress. Since such stress does not operate in vacuo, in this study we sought to determine whether redox-active iron, a potent source of free radicals, was elevated in MCI and preclinical AD as compared to cognitively-intact age-matched control patients. Increased iron was found at the highest levels both in the cortex and cerebellum from the pre-clinical AD/MCI cases. Interestingly, glial accumulations of redox-active iron in the cerebellum were also evident in preclinical AD patients and tended to increase as patients became progressively cognitively impaired. Our findings suggests that an imbalance in iron homeostasis is a precursor to the neurodegenerative processes leading to AD and that iron imbalance is not necessarily unique to affected regions. In fact, an understanding of iron deposition in other regions of the brain may provide insights into neuroprotective strategies. Iron deposition at the preclinical stage of AD may be useful as a diagnostic tool, using iron imaging methods, as well as a potential therapeutic target, through metal ion chelators.

False

CitationGPTRetr606

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid, and selected brain regions: a systematic review and meta-analysis. Abstract of the paper: BACKGROUND The homeostasis and physiological role of iron in Alzheimer's disease (AD) has been debated for decades. Overall, it has been difficult to reach a consensus to prove marked disease-associated changes in the iron content of the AD brain, blood, or cerebrospinal fluid (CSF). OBJECTIVES We sought to contribute to resolve this issue by quantifying the iron content in serum, CSF, and sub-regions of the AD brain. METHODS We conducted a comprehensive systematic meta-analysis and review of multiple observational studies till October 2013 that investigated the iron content in AD serum, CSF, or brain tissue. RESULTS 2,556 publications were screened. Forty-three eligible studies with 1,813 AD patients and 2,401 healthy controls were identified. Twenty-one studies investigated the serum iron in AD while seven and nineteen studies investigated the CSF iron and various brain regions iron respectively. Our meta-analysis showed that serum iron was significant lower in AD than healthy controls. CSF iron appeared not to be affected by AD although more studies are required due to the relative small number of CSF studies reported to date. We critically analyzed iron content in twelve selective brain regions by separated meta-analyses using cross-referenced statistical methods. We found that eight specific brain regions had higher iron concentrations that correlated with the clinical diagnosis of AD in a statistically validated manner. CONCLUSIONS These data provided rigorous statistical support for the model that iron homeostasis was changed in AD patients, including the finding of lower iron in their serum and evidence for iron overload in several specific brain regions.

False

CitationGPTRetr607

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron, zinc and copper in the Alzheimer's disease brain: a quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion. Abstract of the paper: Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer's disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p<0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD.

False

CitationGPTRetr608

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: An anemia of Alzheimer's disease. Abstract of the paper: Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline.

False

CitationGPTRetr609

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer's disease: Evidence of ferroptosis. Abstract of the paper: Iron dyshomeostasis is implicated in Alzheimer's disease (AD) alongside β-amyloid and tau pathologies. Despite the recent discovery of ferroptosis, an iron-dependent form cell death, hitherto, in vivo evidence of ferroptosis in AD is lacking. The present study uniquely adopts an integrated multi-disciplinary approach, combining protein (Western blot) and elemental analysis (total reflection X-ray fluorescence) with metabolomics (1H nuclear magnetic resonance spectroscopy) to identify iron dyshomeostasis and ferroptosis, and possible novel interactions with metabolic dysfunction in age-matched male cognitively normal (CN) and AD post-mortem brain tissue (n = 7/group). Statistical analysis was used to compute differences between CN and AD, and to examine associations between proteins, elements and/or metabolites. Iron dyshomeostasis with elevated levels of ferritin, in the absence of increased elemental iron, was observed in AD. Moreover, AD was characterised by enhanced expression of the light-chain subunit of the cystine/glutamate transporter (xCT) and lipid peroxidation, reminiscent of ferroptosis, alongside an augmented excitatory glutamate to inhibitory GABA ratio. Protein, element and metabolite associations also greatly differed between CN and AD suggesting widespread metabolic dysregulation in AD. We demonstrate iron dyshomeostasis, upregulated xCT (impaired glutathione metabolism) and lipid peroxidation in AD, suggesting anti-ferroptotic therapies may be efficacious in AD.

False

CitationGPTRetr610

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Mild cognitive impairment and Alzheimer patients display different levels of redox-active CSF iron. Abstract of the paper: Oxidative stress constitutes a hallmark of Alzheimer's disease (AD). Recent studies also point to redox active metals such as iron, copper and zinc in mediating oxidative stress in AD pathogenesis. However, the reactivity of cerebrospinal fluid (CSF) iron and its possible correlation with the severity of cognitive decline in both Alzheimer's patients and subjects with mild cognitive impairment (MCI) is still unknown. Here we show that different stages of cognitive and functional impairment are associated with changes in CSF reactive iron. In this work, we compared CSF samples from 56 elders, classified into 4 groups according to their scores on the Clinical Dementia Rating scale (CDR). Total CSF iron was analyzed by atomic absorption spectrometry. Redox-active iron was analyzed by a novel fluorimetric assay. One-way ANOVA was used to test differences in mean values, and Newman-Keuls Multiple Comparison Test was used for multi group comparisons. No difference in total CSF iron was found between different groups. Significant amounts of redox-active iron were found in CSF and their levels correlated with the extent of cognitive impairment. Redox-active CSF iron levels increased with the degree of cognitive impairment from normal to MCI subjects, while AD patients showed an abrupt decrease to levels close to zero. Given the relevance of oxidative damage in neurodegeneration, it might be possible to associate the development of cognitive and functional decline with the presence of redox-active iron in the CSF. The decrease in redox-active iron found in AD patients may represent a terminal situation, whereby the central nervous system attempts to minimize iron-associated toxicity.

False

CitationGPTRetr611

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron in Alzheimer's Disease: From Physiology to Disease Disabilities. Abstract of the paper: Reactive oxygen species (ROS) play a key role in the neurodegeneration processes. Increased oxidative stress damages lipids, proteins, and nucleic acids in brain tissue, and it is tied to the loss of biometal homeostasis. For this reason, attention has been focused on transition metals involved in several biochemical reactions producing ROS. Even though a bulk of evidence has uncovered the role of metals in the generation of the toxic pathways at the base of Alzheimer's disease (AD), this matter has been sidelined by the advent of the Amyloid Cascade Hypothesis. However, the link between metals and AD has been investigated in the last two decades, focusing on their local accumulation in brain areas known to be critical for AD. Recent evidence revealed a relation between iron and AD, particularly in relation to its capacity to increase the risk of the disease through ferroptosis. In this review, we briefly summarize the major points characterizing the function of iron in our body and highlight why, even though it is essential for our life, we have to monitor its dysfunction, particularly if we want to control our risk of AD.

False

CitationGPTRetr612

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron, copper, and iron regulatory protein 2 in Alzheimer's disease and related dementias. Abstract of the paper: Accumulating evidence implicates a role for altered iron and copper metabolism in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, imbalances in the levels of the various forms of iron at different stages of AD have not been examined. In this pilot study we extracted and measured the levels of loosely bound, non-heme and total iron and copper in the frontal cortex and hippocampus of patients with mild-moderate AD (n=3), severe AD (n=8) and dementia with Lewy bodies (DLB, n=6), using graphite furnace atomic absorption spectrometry (GFAAS). Additionally, the expression of iron regulatory protein 2 (IRP2) was examined in relation to the pathological hallmarks of AD and DLB, amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies, by immunohistochemistry. We found significantly decreased loosely bound iron in the hippocampal white matter of mild-moderate and severe AD patients and a trend towards increased non-heme iron in the hippocampal gray matter of severe AD patients. Furthermore, decreased levels of total copper were seen in severe AD and DLB frontal cortex compared to controls, suggesting an imbalance in brain metal levels in both AD and DLB. The decrease in loosely bound iron in mild-moderate AD patients may be associated with myelin breakdown seen in the beginning stages of AD and implicates that iron dysregulation is an early event in AD pathogenesis.

False

CitationGPTRetr613

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron and Ferroptosis as Therapeutic Targets in Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD), one of the most common neurodegenerative diseases worldwide, has a devastating personal, familial, and societal impact. In spite of profound investment and effort, numerous clinical trials targeting amyloid-β, which is thought to have a causative role in the disease, have not yielded any clinically meaningful success to date. Iron is an essential cofactor in many physiological processes in the brain. An extensive body of work links iron dyshomeostasis with multiple aspects of the pathophysiology of AD. In particular, regional iron load appears to be a risk factor for more rapid cognitive decline. Existing iron-chelating agents have been in use for decades for other indications, and there are preliminary data that some of these could be effective in AD. Many novel iron-chelating compounds are under development, some with in vivo data showing potential Alzheimer's disease-modifying properties. This heretofore underexplored therapeutic class has considerable promise and could yield much-needed agents that slow neurodegeneration in AD.

False

CitationGPTRetr614

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron and Alzheimer's Disease: From Pathogenesis to Therapeutic Implications. Abstract of the paper: As people age, iron deposits in different areas of the brain may impair normal cognitive function and behavior. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, and ultimately leads to cell death. There is an imbalance in iron homeostasis in Alzheimer's disease (AD). Excessive iron contributes to the deposition of β-amyloid and the formation of neurofibrillary tangles, which in turn, promotes the development of AD. Therefore, iron-targeted therapeutic strategies have become a new direction. Iron chelators, such as desferoxamine, deferiprone, deferasirox, and clioquinol, have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Given the limitations and side effects of the long-term application of traditional iron chelators, alpha-lipoic acid and lactoferrin, as self-synthesized naturally small molecules, have shown very intriguing biological activities in blocking Aβ-aggregation, tauopathy and neuronal damage. Despite a lack of evidence for any clinical benefits, the conjecture that therapeutic chelation, with a special focus on iron ions, is a valuable approach for treating AD remains widespread.

False

CitationGPTRetr615

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Vitamin B12 levels in Alzheimer's disease: association with clinical features and cytokine production. Abstract of the paper: Alzheimer's disease (AD) has been associated with up-regulation of pro-inflammatory cytokines (e.g., specific gene variants for TNF-alpha; IL-6; IFN-gamma) and low plasma levels of cyanocobalamin (vitamin B12). Our goal was to relate B12 levels to AD symptoms and to expression of pro-inflammatory cytokines. Clinical manifestations were investigated for a case series of fifty-five outpatients using the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). Plasma B12 levels were measured by radioligand binding assay. Basal and PMA-stimulated levels of IFN-gamma, TNF-alpha, and IL-6 were measured by ELISPOT (PBMC culture supernatant). 47 patients were genotyped for APOE. Ten patients (18%) had their B12 levels below < 250 pg/ml. They did not statistically differ from those 45 who had normal levels in most demographic and clinical features; their MMSE scores were lower (14.7 vs 19.6 p=0.03) but not after adjustment for disease duration. A greater basal production of IL-6 was reported in patients who had low B12 levels compared to normal B12 subjects (1333 pg/ml vs 976 p< 0.01); this association was confirmed after controlling for age of onset and APOE genotype. In conclusion, low B12 level is associated with greater production of IL-6 in peripheral blood mononuclear cells. Further research is warranted to elucidate whether this neuroinflammatory effect of cobalamin is implicated in the pathophysiology of AD.

False

CitationGPTRetr616

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Cortical Iron Reflects Severity of Alzheimer's Disease. Abstract of the paper: Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer's disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl's histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex.

False

CitationGPTRetr617

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Decreased plasma iron in Alzheimer's disease is due to transferrin desaturation. Abstract of the paper: Plasma iron levels are decreased in Alzheimer's disease (AD) and associated with an idiopathic anemia. We examined iron-binding plasma proteins from AD patients and healthy controls from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing using size exclusion chromatography-inductively coupled plasma-mass spectrometry. Peak area corresponding to transferrin (Tf) saturation was directly compared to routine pathological testing. We found a significant decrease in transferrin-associated iron in AD that was missed by routine pathological tests of transferrin saturation, and that was able to discriminate between AD and controls. The AD cases showed no significant difference in transferrin concentration, only a decrease in total transferrin-bound iron. These findings support that a previously identified decrease in plasma iron levels in AD patients within the AIBL study is attributable to decreased loading of iron into transferrin, and that this subtle but discriminatory change is not observed through routine pathological testing.

False

CitationGPTRetr618

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Cognitive decline correlates with low plasma concentrations of copper in patients with mild to moderate Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a devastating brain disorder clinically characterised by progressive loss of characteristic cognitive abilities. Increasing evidence suggests a disturbed copper (Cu) homeostasis to be associated with the pathological processes. In the present study we analysed the plasma Cu levels and cognitive abilities using the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog) in 32 patients with mild to moderate AD. Statistical analysis revealed a negative correlation between plasma Cu levels and cognitive decline (r=-0.49; P<0.01). Patients with low plasma Cu (mean 82 +/- SD 9) had significant higher ADAS-cog values (mean 23 +/- SD 7), than patients with medium plasma Cu (mean 110 +/- SD 7), who exhibited lower ADAS-cog scores (mean 16 +/- SD 4; ANOVA, P<0.0001). Despite the fact that all patients had plasma Cu levels within the physiological range between 65 microg and 165 microg/dL, 87.5% of the patients revealed a significant negative correlation between plasma Cu and ADAS-cog. This finding supports the hypothesis of a mild Cu deficiency in most AD patients.

False

CitationGPTRetr619

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nevertheless it is interesting to note that patients diagnosed with ad do not exhibit lower concentrations of cobalt in their blood plasma 52535455 but they have iron disturbances Title of the paper: Iron and Alzheimer's Disease: From Pathology to Imaging. Abstract of the paper: Alzheimer's disease (AD) is a debilitating brain disorder that afflicts millions worldwide with no effective treatment. Currently, AD progression has primarily been characterized by abnormal accumulations of β-amyloid within plaques and phosphorylated tau within neurofibrillary tangles, giving rise to neurodegeneration due to synaptic and neuronal loss. While β-amyloid and tau deposition are required for clinical diagnosis of AD, presence of such abnormalities does not tell the complete story, and the actual mechanisms behind neurodegeneration in AD progression are still not well understood. Support for abnormal iron accumulation playing a role in AD pathogenesis includes its presence in the early stages of the disease, its interactions with β-amyloid and tau, and the important role it plays in AD related inflammation. In this review, we present the existing evidence of pathological iron accumulation in the human AD brain, as well as discuss the imaging tools and peripheral measures available to characterize iron accumulation and dysregulation in AD, which may help in developing iron-based biomarkers or therapeutic targets for the disease.

False

CitationGPTRetr620

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Temporal and regional progression of Alzheimer's disease-like pathology in 3xTg-AD mice. Abstract of the paper: Accumulation of amyloid-β (Aβ) and fibrillary tangles, as well as neuroinflammation and memory loss, are hallmarks of Alzheimer's disease (AD). After almost 15 years from their generation, 3xTg-AD mice are still one of the most used transgenic models of AD. Converging evidence indicates that the phenotype of 3xTg-AD mice has shifted over the years and contradicting reports about onset of pathology or cognitive deficits are apparent in the literature. Here, we assessed Aβ and tau load, neuroinflammation, and cognitive changes in 2-, 6-, 12-, and 20-month-old female 3xTg-AD and nontransgenic (NonTg) mice. We found that ~80% of the mice analyzed had Aβ plaques in the caudal hippocampus at 6 months of age, while 100% of them had Aβ plaques in the hippocampus at 12 months of age. Cortical Aβ plaques were first detected at 12 months of age, including in the entorhinal cortex. Phosphorylated Tau at Ser202/Thr205 and Ser422 was apparent in the hippocampus of 100% of 6-month-old mice, while only 50% of mice showed tau phosphorylation at Thr212/Ser214 at this age. Neuroinflammation was first evident in 6-month-old mice and increased as a function of age. These neuropathological changes were clearly associated with progressive cognitive decline, which was first apparent at 6 months of age and became significantly worse as the mice aged. These data indicate a consistent and predictable progression of the AD-like pathology in female 3xTg-AD mice, and will facilitate the design of future studies using these mice.

False

CitationGPTRetr621

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Microvascular degeneration occurs before plaque onset and progresses with age in 3xTg AD mice. Abstract of the paper: Heart disease and vascular disease positively correlate with the incidence of Alzheimer's disease (AD). Although there is ostensible involvement of dysfunctional cerebrovasculature in AD pathophysiology, the characterization of the specific changes and development of vascular injury during AD remains unclear. In the present study, we established a time-course for the structural changes and degeneration of the angioarchitecture in AD. We used cerebrovascular corrosion cast and µCT imaging to evaluate the geometry, topology, and complexity of the angioarchitecture in the brain of wild type and 3xTg AD mice. We hypothesized that changes to the microvasculature occur early during the disease, and these early identifiable aberrations would be more prominent in the brain subregions implicated in the cognitive decline of AD. Whole-brain analysis of the angioarchitecture indicated early morphological abnormalities and degeneration of microvascular networks in 3xTg AD mice. Our analysis of the hippocampus and cortical subregions revealed microvascular degeneration with onset and progression that was subregion dependent.

False

CitationGPTRetr622

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Staging of Alzheimer's pathology in triple transgenic mice: a light and electron microscopic analysis. Abstract of the paper: The age-related pathological cascade underlying intraneuronal tau formation in 3xTg-AD mice, which harbor the human APP(Swe), PS1(M126V) , and Tau(P301L) gene mutations, remains unclear. At 3 weeks of age, AT180, Alz50, MC1, AT8, and PHF-1 intraneuronal immunoreactivity appeared in the amygdala and hippocampus and at later ages in the cortex of 3xTg-AD mice. AT8 and PHF-1 staining was fixation dependent in young mutant mice. 6E10 staining was seen at all ages. Fluorescent immunomicroscopy revealed CA1 neurons dual stained for 6E10 and Alz50 and single Alz50 immunoreactive neurons in the subiculum at 3 weeks and continuing to 20 months. Although electron microscopy confirmed intraneuronal cytoplasmic Alz50, AT8, and 6E10 reaction product in younger 3xTg-AD mice, straight filaments appeared at 23 months of age in female mice. The present data suggest that other age-related biochemical mechanisms in addition to early intraneuronal accumulation of 6E10 and tau underlie the formation of tau filaments in 3xTg-AD mice.

False

CitationGPTRetr623

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Early increases in soluble amyloid-β levels coincide with cholinergic degeneration in 3xTg-AD mice. Abstract of the paper: Accumulation of amyloid-β peptides (Aβ) and cholinergic degeneration are hallmarks of Alzheimer's disease (AD). In a triple transgenic mouse model of AD (3xTg-AD), soluble Aβ42 levels were detected in the septum by 2 months of age, reaching their highest levels at 3-6 months and decreasing at 12 months. Deficits in the number of septal cholinergic neurons and the length of hippocampal cholinergic axons were observed starting at 4 months in 3xTg-AD mice. Our results show that septal Aβ and septohippocampal cholinergic pathology in 3xTg-AD mice occur at an early stage of disease.

False

CitationGPTRetr624

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: [Morphological analysis of the hippocampal region associated with an innate behaviour task in the transgenic mouse model (3xTg-AD) for Alzheimer disease]. Abstract of the paper: INTRODUCTION Different animal models for Alzheimer disease (AD) have been designed to support the hypothesis that the neurodegeneration (loss of neurons and synapses with reactive gliosis) associated with Aβ and tau deposition in these models is similar to that in the human brain. These alterations produce functional changes beginning with decreased ability to carry out daily and social life activities, memory loss, and neuropsychiatric disorders in general. Neuronal alteration plays an important role in early stages of the disease, especially in the CA1 area of hippocampus in both human and animal models. METHODS Two groups (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis (nest building) and a morphometric analysis of the CA1 region of the dorsal hippocampus. RESULTS The 3xTg-AD mice showed a 50% reduction in nest quality associated with a significant increase in damaged neurons in the CA1 hippocampal area (26%±6%, P<.05) compared to the WT group. CONCLUSIONS The decreased ability to carry out activities of daily living (humans) or nest building (3xTg-AD mice) is related to the neuronal alterations observed in AD. These alterations are controlled by the hippocampus. Post-mortem analyses of the human hippocampus, and the CA1 region in 3xTg-AD mice, show that these areas are associated with alterations in the deposition of Aβ and tau proteins, which start accumulating in the early stages of AD.

False

CitationGPTRetr625

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Primary motor cortex alterations in Alzheimer disease: A study in the 3xTg-AD model. Abstract of the paper: INTRODUCTION In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aβ and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD. METHODS We used female 3xTg-AD mice aged 11 months and compared them to non-transgenic mice of the same age. In both groups, we assessed motor performance (open field test) and neuronal damage in M1 using specific markers: BAM10 (extracellular Aβ aggregates), tau 499 (hyperphosphorylated tau protein), GFAP (astrocytes), and Klüver-Barrera staining (neurons). RESULTS Female 3xTg-AD mice in intermediate stages of the disease displayed motor and cellular alterations associated with Aβ and hyperphosphorylated tau protein deposition in M1. CONCLUSIONS Patients with AD display signs and symptoms of functional impairment from early stages. According to our results, M1 cell damage in intermediate-stage AD affects motor function, which is linked to progression of the disease.

False

CitationGPTRetr626

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology. Abstract of the paper: Alzheimer's disease (AD) is a progressively debilitating brain disorder pathologically defined by extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and synaptic disintegrity. AD has not been widely considered a disease of white matter, but more recent evidence suggests the existence of abnormalities in myelination patterns and myelin attrition in AD-afflicted human brains. Herein, we demonstrate that triple-transgenic AD (3xTg-AD) mice, which harbor the human amyloid precursor protein Swedish mutant transgene, presenilin knock-in mutation, and tau P301L mutant transgene, exhibit significant region-specific alterations in myelination patterns and in oligodendrocyte marker expression profiles at time points preceding the appearance of amyloid and tau pathology. These immunohistochemical signatures are coincident with age-related alterations in axonal and myelin sheath ultrastructure as visualized by comparative electron microscopic examination of 3xTg-AD and nontransgenic mouse brain tissue. Overall, these findings indicate that 3xTg-AD mice represent a viable model in which to examine mechanisms underlying AD-related myelination and neural transmission defects that occur early during presymptomatic stages of the disease process.

False

CitationGPTRetr627

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer's Disease. Abstract of the paper: PURPOSE Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-L-[11C]deprenyl ([11C]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i.e., two well-established markers of astrogliosis, during Aβ pathology progression. PROCEDURES APPArcSwe mice (n = 37) and wild-type (WT) control mice (n = 23), 2-16-month old, were used to investigate biomarkers of astrogliosis. The radioligand, [11C]DED, was used as an in vivo marker while GFAP, vimentin, and MAO-B were used to investigate astrogliosis and macrophage-associated lectin (Mac-2) to investigate microglia/macrophage activation by immunohistochemistry of the mouse brain. Aβ and GFAP levels were also measured with ELISA in brain homogenates. RESULTS The intrabrain levels of aggregated Aβ and reactive astrocytes were found to be elevated in APPArcSwe compared with WT mice. GFAP and vimentin expression increased with age, i.e., with Aβ pathology, in the APPArcSwe mice. This was not the case for in vivo marker [11C]DED that showed elevated binding of the same magnitude in APPArcSwe mice compared with WT mice at both 8 and 16 months. Further, immunohistochemistry indicated that there was limited co-expression of MAO-B and GFAP. CONCLUSIONS MAO-B levels are increased early in Aβ pathology progression, while GFAP and vimentin appear to increase later, most likely as a consequence of abundant Aβ plaque formation. Thus, [11C]DED is a useful PET radioligand for the detection of changes in MAO-B at an early stage of AD progression but does not measure the total extent of astrogliosis at advanced stages of Aβ pathology.

False

CitationGPTRetr628

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Early Stage Alterations in White Matter and Decreased Functional Interhemispheric Hippocampal Connectivity in the 3xTg Mouse Model of Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is characterized in the late stages by amyloid-β (Aβ) plaques and neurofibrillary tangles. Nevertheless, recent evidence has indicated that early changes in cerebral connectivity could compromise cognitive functions even before the appearance of the classical neuropathological features. Diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) and volumetry were performed in the triple transgenic mouse model of AD (3xTg-AD) at 2 months of age, prior to the development of intraneuronal plaque accumulation. We found the 3xTg-AD had significant fractional anisotropy (FA) increase and radial diffusivity (RD) decrease in the cortex compared with wild-type controls, while axial diffusivity (AD) and mean diffusivity (MD) were similar. Interhemispheric hippocampal connectivity was decreased in the 3xTg-AD while connectivity in the caudate putamen (CPu) was similar to controls. Most surprising, ventricular volume in the 3xTg-AD was four times larger than controls. The results obtained in this study characterize the early stage changes in interhemispheric hippocampal connectivity in the 3xTg-AD mouse that could represent a translational biomarker to human models in preclinical stages of the AD.

False

CitationGPTRetr629

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice. Abstract of the paper: BACKGROUND Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD)-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD) harbors three AD-related genetic loci: human PS1M146V, human APPswe, and human tauP301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported. METHODS AND RESULTS In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation. CONCLUSION These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to examine stage-specific disease mechanisms and/or novel therapeutic interventions for AD.

False

CitationGPTRetr630

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: A longitudinal multimodal in vivo molecular imaging study of the 3xTg-AD mouse model shows progressive early hippocampal and taurine loss. Abstract of the paper: The understanding of the natural history of Alzheimer's disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and novel object recognition tests. Molecular characterization evaluated hippocampal levels of amyloid β (Aβ) and hyperphosphorylated tau. Magnetic resonance imaging (MRI) included assessment of hippocampal structural integrity, blood-brain barrier (BBB) permeability and neurospectroscopy to determine levels of the endogenous neuroprotector taurine. Longitudinal brain amyloid accumulation was assessed using 11C Pittsburgh compound B positron emission tomography (PET), and neuroinflammation/microglia activation was investigated using 11C-PK1195. We found altered locomotor activity at months 4/8 and 16 months and recognition memory impairment at all time points. Substantial early reduction of hippocampal volume started at month 4 and progressed over 8/12 and 16 months. Hippocampal taurine levels were significantly decreased in the hippocampus at months 4/8 and 16. No differences were found for amyloid and neuroinflammation with PET, and BBB was disrupted only at month 16. In summary, 3xTg-AD mice showed exploratory and recognition memory impairments, early hippocampal structural loss, increased Aβ and hyperphosphorylated tau and decreased levels of taurine. In sum, the 3xTg-AD animal model mimics pathological and neurobehavioral features of AD, with early-onset recognition memory loss and MRI-documented hippocampal damage. The early-onset profile suggests temporal windows and opportunities for therapeutic intervention, targeting endogenous neuroprotectors such as taurine.

False

CitationGPTRetr631

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease. Abstract of the paper: The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Aβ (amyloid β-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to Aβ accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.

False

CitationGPTRetr632

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo. Abstract of the paper: Mouse Alzheimer's disease (AD) models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct') and long-latency (presumably polysynaptic: 're-entrant') responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice could be due to the development of an abnormal hyper-excitable state in the hippocampal formation.

False

CitationGPTRetr633

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer's Disease. Abstract of the paper: Animal models of disease are valuable resources for investigating pathogenic mechanisms and potential therapeutic interventions. However, for complex disorders such as Alzheimer's disease (AD), the generation and availability of innumerous distinct animal models present unique challenges to AD researchers and hinder the success of useful therapies. Here, we conducted an in-depth analysis of the 3xTg-AD mouse model of AD across its lifespan to better inform the field of the various pathologies that appear at specific ages, and comment on drift that has occurred in the development of pathology in this line since its development 20 years ago. This modern characterization of the 3xTg-AD model includes an assessment of impairments in long-term potentiation followed by quantification of amyloid beta (Aβ) plaque burden and neurofibrillary tau tangles, biochemical levels of Aβ and tau protein, and neuropathological markers such as gliosis and accumulation of dystrophic neurites. We also present a novel comparison of the 3xTg-AD model with the 5xFAD model using the same deep-phenotyping characterization pipeline and show plasma NfL is strongly driven by plaque burden. The results from these analyses are freely available via the AD Knowledge Portal (https://modeladexplorer.org/). Our work demonstrates the utility of a characterization pipeline that generates robust and standardized information relevant to investigating and comparing disease etiologies of current and future models of AD.

False

CitationGPTRetr634

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer's Disease. Abstract of the paper: In this study, we aimed to disclose the impact of amyloid-β toxicity and tau pathology on astrocyte swelling, their volume recovery and extracellular space (ECS) diffusion parameters, namely volume fraction (α) and tortuosity (λ), in a triple transgenic mouse model of Alzheimer's disease (3xTg-AD). Astrocyte volume changes, which reflect astrocyte ability to take up ions/neurotransmitters, were quantified during and after exposure to hypo-osmotic stress, or hyperkalemia in acute hippocampal slices, and were correlated with alterations in ECS diffusion parameters. Astrocyte volume and ECS diffusion parameters were monitored during physiological aging (controls) and during AD progression in 3-, 9-, 12- and 18-month-old mice. In the hippocampus of controls α gradually declined with age, while it remained unaffected in 3xTg-AD mice during the entire time course. Moreover, age-related increases in λ occurred much earlier in 3xTg-AD animals than in controls. In 3xTg-AD mice changes in α induced by hypo-osmotic stress or hyperkalemia were comparable to those observed in controls, however, AD progression affected α recovery following exposure to both. Compared to controls, a smaller astrocyte swelling was detected in 3xTg-AD mice only during hyperkalemia. Since we observed a large variance in astrocyte swelling/volume regulation, we divided them into high- (HRA) and low-responding astrocytes (LRA). In response to hyperkalemia, the incidence of LRA was higher in 3xTg-AD mice than in controls, which may also reflect compromised K+ and neurotransmitter uptake. Furthermore, we performed single-cell RT-qPCR to identify possible age-related alterations in astrocytic gene expression profiles. Already in 3-month-old 3xTg-AD mice, we detected a downregulation of genes affecting the ion/neurotransmitter uptake and cell volume regulation, namely genes of glutamate transporters, α2β2 subunit of Na+/K+-ATPase, connexin 30 or Kir4.1 channel. In conclusion, the aged hippocampus of 3xTg-AD mice displays an enlarged ECS volume fraction and an increased number of obstacles, which emerge earlier than in physiological aging. Both these changes may strongly affect intercellular communication and influence astrocyte ionic/neurotransmitter uptake, which becomes impaired during aging and this phenomenon is manifested earlier in 3xTg-AD mice. The increased incidence of astrocytes with limited ability to take up ions/neurotransmitters may further add to a cytotoxic environment.

False

CitationGPTRetr635

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Motor deficits in 16-month-old male and female 3xTg-AD mice. Abstract of the paper: Motor deficits are some of the most prevalent non-cognitive symptoms of Alzheimer's disease (AD) with patients showing impairments in speech, gait and fine motor skills. We investigated motor behaviour in 16-month-old male and female 3xTg-AD mice and their B6129SF2 wildtype (WT) controls. The 3xTg-AD mice develop extracellular Aβ plaques and tau tangles in the hippocampus and motor cortex between 6 and 9 months of age. Previously we showed that at 6 months of age, 3xTg-AD mice performed better on tests of motor coordination and motor learning than WT mice. The aim of our experiment was to use a battery of motor behaviour tests to determine if this superior motor performance was present in older mice. On the Rotarod, the aged 3xTg-AD mice showed better motor coordination and learning than WT mice. Although females performed better than males, this sex difference was confounded by body weight as females weighed less than males. There were no significant genotype or sex differences on the wire hang or grid suspension tasks, nor in stride length or stride width, but 3xTg-AD mice performed worse than WT mice on the balance beam. In comparison to the 6-month-old mice, an age-related decline in most aspects of motor behaviour was apparent. These results indicate that different sub-domains of motor function are affected differently in the 3xTg-AD mice and that aging does not have the same effect on all motor behaviours.

False

CitationGPTRetr636

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study. Abstract of the paper: Recent mouse studies of the presymptomatic stage of Alzheimer's disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFα contributes to increased Aβ production from the Aβ precursor protein (APP), we assessed a putative correlation between APP/Aβ and TNFα during the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβ was not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFα and APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD.

False

CitationGPTRetr637

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Pathological Alterations of Tau in Alzheimer's Disease and 3xTg-AD Mouse Brains. Abstract of the paper: Microtubule-associated protein tau in Alzheimer's disease (AD) brain is hyperphosphorylated, truncated, and aggregated into neurofibrillary tangles. Oligomeric and hyperphosphorylated tau (Oligo-tau) isolated from AD brain captures and templates normal tau into filaments both in vitro and in vivo; this prion-like activity is believed to be responsible for the progression of neurofibrillary pathology in AD. The 3xTg-AD mouse model develops both Aβ and tau pathologies and thus gains popularity in preclinical studies of AD. Despite the histopathological similarity of the 3xTg-AD model to AD, biochemical authenticity of tau alterations in this model remains elusive. To investigate the biochemical basis of tau pathology in 3xTg-AD brain, we here compared pathological alterations of tau in the aged 3xTg-AD brain to those in AD brain. We found that in contrast to substantial high molecular weight smear tau (HMW-tau) lacking the N-terminal portion and hyperphosphorylated at multiple sites in AD brain, tau in 3xTg-AD mouse brain showed no detectable HMW-tau or truncation but slightly increased phosphorylation when normalized with total tau. In addition, AT8 immunostaining exhibited filamentous tau inclusions in AD brain, but predominantly truffle-like morphology in aged 3xTg-AD mouse brain. Further, Oligo-tau isolated from 3xTg-AD mice showed minimal potency in capturing tau in vitro and seeding tau aggregation in cultured cells when compared to AD Oligo-tau. These findings suggest that the alterations of tau in 3xTg-AD mouse brain differ from those in AD brain. In 3xTg-AD mice, the lack of N-terminal truncation, scarce SDS/reducing reagent-resistant HMW-tau, and minimal hyperphosphorylation may collectively result in low potency in prion-like activity of the Oligo-tau.

False

CitationGPTRetr638

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: iTRAQ analysis of complex proteome alterations in 3xTgAD Alzheimer's mice: understanding the interface between physiology and disease. Abstract of the paper: Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid beta-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders.

False

CitationGPTRetr639

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the astrocytic degeneration in the hippocampus within ad progression was shown previously for 9monthold 3xtgad mice with both aβ and tau pathologies 65666768 and in the postmortem cortexes of ad patients Title of the paper: Astrocytic cytoskeletal atrophy in the medial prefrontal cortex of a triple transgenic mouse model of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the loss of cognitive functions, reflecting pathological damage to the medial prefrontal cortex (mPFC) as well as to the hippocampus and the entorhinal cortex. Astrocytes maintain the internal homeostasis of the CNS and are fundamentally involved in neuropathological processes, including AD. Here, we analysed the astrocytic cytoskeletal changes within the mPFC of a triple transgenic mouse model of AD (3 × Tg-AD) by measuring the surface area and volume of glial fibrillary acidic protein (GFAP)-positive profiles in relation to the build-up and presence of amyloid-β (Aβ), and compared the results with those found in non-transgenic control animals at different ages. 3 × Tg-AD animals showed clear astroglial cytoskeletal atrophy, which appeared at an early age (3 months; 33% and 47% decrease in GFAP-positive surface area and volume, respectively) and remained throughout the disease progression at 9, 12 and 18 months old (29% and 36%; 37% and 35%; 43% and 37%, respectively). This atrophy was independent of Aβ accumulation, as only a few GFAP-positive cells were localized around Aβ aggregates, which suggests no direct relationship with Aβ toxicity. Thus, our results indicate that the progressive reduction in astrocytic branching and domain in the mPFC can account for the integrative dysfunction leading to the cognitive deficits and memory disturbances observed in AD.

False

CitationGPTRetr640

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglial polarization: novel therapeutic mechanism against Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease that results in progressive dementia, and exhibits high disability and fatality rates. Recent evidence has demonstrated that neuroinflammation is critical in the pathophysiological processes of AD, which is characterized by the activation of microglia and astrocytes. Under different stimuli, microglia are usually activated into two polarized states, termed the classical 'M1' phenotype and the alternative 'M2' phenotype. M1 microglia are considered to promote inflammatory injury in AD; in contrast, M2 microglia exert neuroprotective effects. Imbalanced microglial polarization, in the form of excessive activation of M1 microglia and dysfunction of M2 microglia, markedly promotes the development of AD. Furthermore, an increasing number of studies have shown that the transition of microglia from the M1 to M2 phenotype could potently alleviate pathological damage in AD. Hence, this article reviews the current knowledge regarding the role of microglial M1/M2 polarization in the pathophysiology of AD. In addition, we summarize several approaches that protect against AD by altering the polarization states of microglia. This review aims to contribute to a better understanding of the pathogenesis of AD and, moreover, to explore the potential of novel drugs for the treatment of AD in the future.

False

CitationGPTRetr641

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglia Polarization in Alzheimer's Disease: Mechanisms and a Potential Therapeutic Target. Abstract of the paper: Neuroinflammation regulated by microglia is one of the important factors involved in the pathogenesis of Alzheimer's disease (AD). Activated microglia exhibited phenotypes termed as M1 and M2 phenotypes separately. M1 microglia contribute to the development of inflammation via upregulating pro-inflammatory cytokines, while M2 microglia exert anti-inflammation effects through enhancing the expression of anti-inflammation factors. Moreover, M1 and M2 microglia could be mutually transformed under various conditions. Both M1 and M2 microglia are implicated in AD. Amyloid-β (Aβ) and hyperphosphorylated tau are two major components of AD pathological hallmarks, neuritic plaques, and neurofibrillary tangles. Both Aβ and hyperphosphorylated tau were involved in microglial activation and subsequent inflammation, which further contribute to neuronal and synaptic loss in AD. In this review, we summarized the roles of M1 and M2 microglia in AD and underlying mechanisms, which will provide an insight into the role of microglia in the pathogenesis of AD and highlight the therapeutic potential of modulating microglia.

False

CitationGPTRetr642

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Diversity and plasticity of microglial cells in psychiatric and neurological disorders. Abstract of the paper: Recent advanced immunological analyses have revealed that the diversity and plasticity of macrophages lead to the identification of functional polarization states (classically activated M1 type and alternatively activated M2 type) which are dependent on the extracellular environment. M1 and M2 polarization states of macrophages play an important role in controlling the balance between pro-inflammatory and anti-inflammatory conditions. Microglial cells are resident mononuclear phagocytes in the central nervous system (CNS), express several macrophage-associated markers, and appear to display functional polarization states similar to macrophages. Like M1 macrophages, M1 polarized microglia can produce pro-inflammatory cytokines and mediators such as interleukin (IL) 1β, IL-6, tumor necrosis factor-α, CC-chemokine ligand 2, nitric oxide, and reactive oxygen species, suggesting that these molecules contribute to dysfunction of neural network in the CNS. On the other hand, M2 polarized microglia can produce anti-inflammatory cytokine, IL-10 and express several receptors that are implicated in inhibiting inflammation and restoring homeostasis. In this review, we summarize the diversity, plasticity, and immunoregulatory functions of M1 and M2 microglia in psychiatric and neurological disorders. Based on these aspects, we propose a contribution of imbalance between M1 and M2 polarization of microglia in bipolar disorder, obesity, amyotrophic lateral sclerosis, and Rett syndrome. Consequently, molecules that normalize the imbalance between M1 and M2 microglial polarization states may provide a beneficial therapeutic target for the treatment of these disorders.

False

CitationGPTRetr643

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. Abstract of the paper: The concept of multiple macrophage activation states is not new. However, extending this idea to resident tissue macrophages, like microglia, has gained increased interest in recent years. Unfortunately, the research on peripheral macrophage polarization does not necessarily translate accurately to their central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory cytokines can polarize microglia to distinct activation states, the specific functions of these states is still an area of intense debate. This review examines the multiple possible activation states microglia can be polarized to. This is followed by a detailed description of microglial polarization and the functional relevance of this process in both acute and chronic CNS disease models described in the literature. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.

False

CitationGPTRetr644

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains. Abstract of the paper: Inflammatory responses in the brain, which can be demonstrated by changes in properties of microglia, the brain-resident macrophages, are a common feature of human neurodegenerative diseases. Different monocyte/macrophage phenotypes have been defined by changes in expression of cytokines, receptors and other markers as a response to different classes of stimuli. Monocytes, macrophages and microglia can have a range of phenotypes with associated properties depending on their microenvironment. Macrophage/microglia polarization states have been defined as classical activation (M1), alternative activation (M2a), type II alternative activation (M2b) or acquired deactivation (M2c). Available markers for identifying microglial phenotypes in human brains are still limited; those available provide incomplete information on the functions or polarization states of microglia observed in tissues from diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. The most widely used marker to describe activated microglia in human brains, particularly diseased brains, has been HLA-DR, the major histocompatibility complex II protein. HLA-DR-positive microglia can have a wide range of activation morphologies that are affected not only by disease pathology, but also by their differentiation states and brain regions. Two other widely used markers to identify microglia in human brains are ionized calcium binding adaptor molecule-1 and CD68. Although their expression changes in diseased brains, these markers do not show specificity for different phenotypes. Over the years there have been studies with additional markers that attempt to further define microglial properties, particularly in Alzheimer's disease brains. Most studies have employed immunohistochemical techniques to identify microglia in tissue sections, but recent advances in this field have allowed gene expression profiling of microglia upon immediate isolation from brains. We will review which markers might better define different activation phenotypes of microglia in human brains and whether they fit into current microglial polarization schemes.

False

CitationGPTRetr645

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: A richer and more diverse future for microglia phenotypes. Abstract of the paper: Microglia are the only resident innate immune cells derived from the mesoderm in the nerve tissue. They play a role in the development and maturation of the central nervous system (CNS). Microglia mediate the repair of CNS injury and participate in endogenous immune response induced by various diseases by exerting neuroprotective or neurotoxic effects. Traditionally, microglia are considered to be in a resting state, the M0 type, under physiological conditions. In this state, they perform immune surveillance by constantly monitoring pathological responses in the CNS. In the pathological state, microglia undergo a series of morphological and functional changes from the M0 state and eventually polarize into classically activated microglia (M1) and alternatively activated microglia (M2). M1 microglia release inflammatory factors and toxic substances to inhibit pathogens, while M2 microglia exert neuroprotective effects by promoting nerve repair and regeneration. However, in recent years, the view regarding M1/M2 polarization of microglia has gradually changed. According to some researchers, the phenomenon of microglia polarization is not yet confirmed. The M1/M2 polarization term is used for a simplified description of its phenotype and function. Other researchers believe that the microglia polarization process is rich and diverse, and consequently, the classification method of M1/M2 has limitations. This conflict hinders the academic community from establishing more meaningful microglia polarization pathways and terms, and therefore, a careful revision of the concept of microglia polarization is required. The present article briefly reviews the current consensus and controversy regarding microglial polarization typing to provide supporting materials for a more objective understanding of the functional phenotype of microglia.

False

CitationGPTRetr646

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Comparison of polarization properties of human adult microglia and blood-derived macrophages. Abstract of the paper: Both microglia, the resident myeloid cells of the CNS parenchyma, and infiltrating blood-derived macrophages participate in inflammatory responses in the CNS. Macrophages can be polarized into M1 and M2 phenotypes, which have been linked to functional properties including production of inflammation association molecules and phagocytic activity. We compare phenotypic and functional properties of microglia derived from the adult human CNS with macrophages derived from peripheral blood monocytes in response to M1 and M2 polarizing conditions. Under M1 conditions, microglia and macrophages upregulate expression of CCR7 and CD80. M2 treatment of microglia-induced expression of CD209 but not additional markers CD23, CD163, and CD206 expressed by M2 macrophages. M1-polarizing conditions induced production of IL-12p40 by both microglia and macrophages; microglia produced higher levels of IL-10 under M1 conditions than did macrophages. Under M2 conditions, microglia ± LPS produced comparable levels of IL-10 under M1 conditions whereas IL-10 was induced by LPS in M2 macrophages. Myelin phagocytosis was greater in microglia than macrophages under all conditions; for both cell types, activity was higher for M2 cells. Our findings delineate distinctive properties of microglia compared with exogenous myeloid cells in response to signals derived from an inflammatory environment in the CNS.

False

CitationGPTRetr647

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglia Polarization From M1 to M2 in Neurodegenerative Diseases. Abstract of the paper: Microglia-mediated neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Microglia can be categorized into two opposite types: classical (M1) or alternative (M2), though there's a continuum of different intermediate phenotypes between M1 and M2, and microglia can transit from one phenotype to another. M1 microglia release inflammatory mediators and induce inflammation and neurotoxicity, while M2 microglia release anti-inflammatory mediators and induce anti-inflammatory and neuroprotectivity. Microglia-mediated neuroinflammation is considered as a double-edged sword, performing both harmful and helpful effects in neurodegenerative diseases. Previous studies showed that balancing microglia M1/M2 polarization had a promising therapeutic prospect in neurodegenerative diseases. We suggest that shifting microglia from M1 to M2 may be significant and we focus on the modulation of microglia polarization from M1 to M2, especially by important signal pathways, in neurodegenerative diseases.

False

CitationGPTRetr648

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders. Abstract of the paper: Recent neuroscience research has established the adult brain as a dynamic organ having a unique ability to undergo changes with time. Neuroglia, especially microglia and astrocytes, provide dynamicity to the brain. Activation of these glial cells is a major component of the neuroinflammatory responses underlying brain injury and neurodegeneration. Glial cells execute functional reaction programs in response to diverse microenvironmental signals manifested by neuropathological conditions. Activated microglia exist along a continuum of two functional states of polarization namely M1-type (classical/proinflammatory activation) and M2-type (alternative/anti-inflammatory activation) as in macrophages. The balance between classically and alternatively activated microglial phenotypes influences disease progression in the CNS. The classically activated state of microglia drives the neuroinflammatory response and mediates the detrimental effects on neurons, whereas in their alternative activation state, which is apparently a beneficial activation state, the microglia play a crucial role in tissue maintenance and repair. Likewise, in response to immune or inflammatory microenvironments astrocytes also adopt neurotoxic or neuroprotective phenotypes. Reactive astrocytes exhibit two distinctive functional phenotypes defined by pro- or anti-inflammatory gene expression profile. In this review, we have thoroughly covered recent advances in the understanding of the functional polarization of brain and peripheral glia and its implications in neuroinflammation and neurological disorders. The identifiable phenotypes adopted by neuroglia in response to specific insult or injury can be exploited as promising diagnostic markers of neuroinflammatory diseases. Furthermore, harnessing the beneficial effects of the polarized glia could undoubtedly pave the way for the formulation of novel glia-based therapeutic strategies for diverse neurological disorders.

False

CitationGPTRetr649

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Role of Microglia in Neurological Disorders and Their Potentials as a Therapeutic Target. Abstract of the paper: Microglia are resident macrophage-like immune cells in the central nervous system (CNS) and play a vital role in both physiological and pathological conditions, including restoring the integrity of the CNS and promoting the progression of neurodegenerative disorders. Upon stimulation, microglia typically convert from a surveillant to an activated phenotype. The major function of microglia is to maintain homeostasis and normal function of the CNS, both during development and in response to CNS injury. Microglia regulate multiple aspects of inflammation, such as repair, cytotoxicity, regeneration, and immunosuppression due to their different kind of activation states or phenotypes. Although microglia are involved in almost all neurodegenerative disorders, the mechanisms for microglial activation and their potential contributions to neuronal degeneration remain a matter of intense debate. In inflammatory process of the CNS, polarized M1 microglia can produce proinflammatory cytokines, neurotoxic molecules, which contribute to dysfunction of neural network and promoting inflammation reaction, whereas polarized M2 microglia secrete antiinflammatory mediators and neurotrophic factors that are involved in restoring homeostasis. Modulation of microglial activation for therapeutic purposes might be realized via suppressing the deleterious effects of these cells, while simultaneously retaining their protective functions. Here, we summarize the functions of microglia and discuss dual role of microglia in neurodegenerative diseases as well as multiple sclerosis.

False

CitationGPTRetr650

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Treatment targets for M2 microglia polarization in ischemic stroke. Abstract of the paper: As the first line of defense in the nervous system, resident microglia are the predominant immune cells in the brain. In diseases of the central nervous system such as stroke, Alzheimer's disease, and Parkinson's disease, they often cause inflammation or phagocytosis; however, some studies have found that despite the current controversy over M1, M2 polarization could be beneficial. Ischemic stroke is the third most common cause of death in humans. Patients who survive an ischemic stroke might experience a clear decline in their quality of life, owing to conditions such as hemiplegic paralysis and aphasia. After stroke, the activated microglia become a double-edged sword, with distinct phenotypic changes to the deleterious M1 and neuroprotective M2 types. Therefore, methods for promoting the differentiation of microglia into the M2 polarized form to alleviate harmful reactions after stroke have become a topic of interest in recent years. Subsequently, the discovery of new drugs related to M2 polarization has enabled the realization of targeted therapies. In the present review, we discussed the neuroprotective effects of microglia M2 polarization and the potential mechanisms and drugs by which microglia can be transformed into the M2 polarized type after stroke.

False

CitationGPTRetr651

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglial M1/M2 polarization and metabolic states. Abstract of the paper: Microglia are critical nervous system-specific immune cells serving as tissue-resident macrophages influencing brain development, maintenance of the neural environment, response to injury and repair. As influenced by their environment, microglia assume a diversity of phenotypes and retain the capability to shift functions to maintain tissue homeostasis. In comparison with peripheral macrophages, microglia demonstrate similar and unique features with regards to phenotype polarization, allowing for innate immunological functions. Microglia can be stimulated by LPS or IFN-γ to an M1 phenotype for expression of pro-inflammatory cytokines or by IL-4/IL-13 to an M2 phenotype for resolution of inflammation and tissue repair. Increasing evidence suggests a role of metabolic reprogramming in the regulation of the innate inflammatory response. Studies using peripheral immune cells demonstrate that polarization to an M1 phenotype is often accompanied by a shift in cells from oxidative phosphorylation to aerobic glycolysis for energy production. More recently, the link between polarization and mitochondrial energy metabolism has been considered in microglia. Under these conditions, energy demands would be associated with functional activities and cell survival and thus, may serve to influence the contribution of microglia activation to various neurodegenerative conditions. This review examines the polarization states of microglia and their relationship to mitochondrial metabolism. Additional supporting experimental data are provided to demonstrate mitochondrial metabolic shifts in primary microglia and the BV-2 microglia cell line induced under LPS (M1) and IL-4/IL-13 (M2) polarization.

False

CitationGPTRetr652

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases. Abstract of the paper: Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS). In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.

False

CitationGPTRetr653

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglia in Alzheimer's disease. Abstract of the paper: Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. Microglia express a wide range of receptors that act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition to their classical immune cell function, microglia act as guardians of the brain by promoting phagocytic clearance and providing trophic support to ensure tissue repair and maintain cerebral homeostasis. Conditions associated with loss of homeostasis or tissue changes induce several dynamic microglial processes, including changes of cellular morphology, surface phenotype, secretory mediators, and proliferative responses (referred to as an "activated state"). Activated microglia represent a common pathological feature of several neurodegenerative diseases, including Alzheimer's disease (AD). Cumulative evidence suggests that microglial inflammatory activity in AD is increased while microglial-mediated clearance mechanisms are compromised. Microglia are perpetually engaged in a mutual interaction with the surrounding environment in CNS; thus, diverse microglial reactions at different disease stages may open new avenues for therapeutic intervention and modification of inflammatory activities. In this Review, the role of microglia in the pathogenesis of AD and the modulation of microglia activity as a therapeutic modality will be discussed.

False

CitationGPTRetr654

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Alternatively activated microglia and macrophages in the central nervous system. Abstract of the paper: Macrophages are important players in the fight against viral, bacterial, fungal and parasitic infections. From a resting state they may undertake two activation pathways, the classical known as M1, or the alternative known as M2. M1 markers are mostly mediators of pro-inflammatory responses whereas M2 markers emerge for resolution and cleanup. Microglia exerts in the central nervous system (CNS) a function similar to that of macrophages in the periphery. Microglia activation and proliferation occurs in almost any single pathology affecting the CNS. Often microglia activation has been considered detrimental and drugs able to stop microglia activation were considered for the treatment of a variety of diseases. Cumulative evidence shows that microglia may undergo the alternative activation pathway, express M2-type markers and contribute to neuroprotection. This review focuses on details about the role of M2 microglia and in the approaches available for its identification. Approaches to drive the M2 phenotype and data on its potential in CNS diseases are also reviewed.

False

CitationGPTRetr655

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain. Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline of cognitive function. There is no therapy that can halt or reverse its progression. Contemporary research suggests that age-dependent neuroinflammatory changes may play a significant role in the decreased neurogenesis and cognitive impairments in AD. The innate immune response is characterized by pro-inflammatory (M1) activation of macrophages and subsequent production of specific cytokines, chemokines, and reactive intermediates, followed by resolution and alternative activation for anti-inflammatory signaling (M2a) and wound healing (M2c). We propose that microglial activation phenotypes are analogous to those of macrophages and that their activation plays a significant role in regulating neurogenesis in the brain. Microglia undergo a switch from an M2- to an M1-skewed activation phenotype during aging. This review will assess the neuroimmunological studies that led to characterization of the different microglial activation states in AD mouse models. It will also discuss the roles of microglial activation on neurogenesis in AD and propose anti-inflammatory molecules as exciting therapeutic targets for research. Molecules such as interleukin-4 and CD200 have proven to be important anti-inflammatory mediators in the regulation of neuroinflammation in the brain, which will be discussed in detail for their therapeutic potential.

False

CitationGPTRetr656

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Abstract of the paper: One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

False

CitationGPTRetr657

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglia/macrophage polarization: Fantasy or evidence of functional diversity? Abstract of the paper: Microglia and non-parenchymal macrophages are increasingly recognized to play critical roles in the central nervous system (CNS) health and disease. Accumulating evidence suggests that these mononuclear phagocytes do not constitute stereotypical cell populations, but rather polarize into a variety of phenotypes at different stages of CNS development, stresses, and diseases. This commentary aims to discuss our current consensus and controversy on microglia/macrophage phenotypes. Collective single-cell level evidence validates the concept of microglia/macrophage polarization, while suggests multi-polarity instead of dichotomic polarization. Characterizing the functions of a specific microglia/macrophage phenotype is challenging yet essential to translate our scientific discoveries into clinical application.

True

CitationGPTRetr658

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglia in Alzheimer's disease: A multifaceted relationship. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting elderly people worldwide, which is mainly characterized by cerebral amyloid-beta (Aβ) plaque deposition and neurofibrillary tangle formation. The interest in microglia arose from the overwhelming experimental evidence that outlined a key role of neuroinflammation in AD pathology. Microglia constitute the powerhouse of the innate immune system in the brain. It is now widely accepted that microglia are myeloid-derived cells that infiltrate the developing brain at the early embryonic stages, and acquire a highly ramified phenotype postnatally. Microglia use these dynamic ramifications as sentinels to sense and detect any occurring alteration in brain homeostasis. Once a danger signal is detected, microglia get activated by acquiring a less ramified phenotype, and mount adequate responses that range from phagocyting cell debris to secreting inflammatory and trophic factors. Earlier reports have demonstrated, unequivocally, that microglia surround Aβ plaques and internalize Aβ microaggregates. However, the implication of these observations in AD pathology, and consequently treatment, is still a matter of debate. Nonetheless, targeting the activity of these cells constituted a convergent point in this debate. Unfortunately, the conflicting experimental findings obtained following the modulation of microglial activity in AD, further fueled the debate. This review aims at providing an overview regarding what we know about the implication of microglia in AD pathology, and treatment. The emerging role of monocytes is also discussed.

False

CitationGPTRetr659

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: activated microglia can be classified into m1 polarization status with a proinflammatory response and m2 polarization status with an antiinflammatory response and phagocytic function the m2 polarization status of microglia plays an important role in clearing aβ plaques and alleviating neurotoxicity Title of the paper: Microglia Function in the Central Nervous System During Health and Neurodegeneration. Abstract of the paper: Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.

False

CitationGPTRetr660

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Alzheimer's Disease in the Latino Community: Intersection of Genetics and Social Determinants of Health. Abstract of the paper: Alzheimer's disease (AD) is the most common type of dementia among individuals 65 or older. There are more than 5 million diagnosed cases in the US alone and this number is expected to triple by 2050. Therefore, AD has reached epidemic proportions with significant socioeconomic implications. While aging in general is the greatest risk factor for AD, several additional demographic factors that have contributed to the rise in AD in the US are under study. One such factor is associated with the relatively fast growth of the Latino population. Several reports indicate that AD is more prevalent among blacks and Latinos. However, the reason for AD disparity among different ethnic groups is still poorly understood and highly controversial. The Latino population is composed of different groups based on nationality, namely South and Central America, Mexico, and Caribbean Hispanics. This diversity among the Latino population represents an additional challenge since there are distinct characteristics associated with AD and comorbidities. In this review, we aim to bring attention to the intersection between social determinants of health and genetic factors associated with AD within the Latino community. We argue that understanding the interplay between identified social determinants of health, co-morbidities, and genetic factors could lead to community empowerment and inclusiveness in research and healthcare services, contributing to improved diagnosis and treatment of AD patients. Lastly, we propose that inserting a neuroethics perspective could help understand key challenges that influence healthcare disparities and contribute to increased risk of AD among Latinos.

False

CitationGPTRetr661

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Re-examining ethnic differences in concerns, knowledge, and beliefs about Alzheimer's disease: results from a national sample. Abstract of the paper: OBJECTIVE This study aims to evaluate ethnic group differences in concerns, knowledge, and beliefs about Alzheimer's disease (AD) in three ethnic groups of older adults (White, Latino, and Black). METHODS The Health and Retirement Study is a US national representative study of older adults over the age of 50 years and their spouse of any age. The study is based on the 2010 wave. RESULTS Analysis is based on data from 939 White, 120 Latino, and 171 Black respondents who completed a special module about AD concerns, knowledge, and beliefs. There were significant ethnic differences on 7 of 13 items. However, after the adjustment for education, gender, age, having a family member with AD, depressive symptoms, and medical comorbidity, only four items showed significant ethnic group differences; relative to White respondents, Black respondents were less likely to report that having a parent or a sibling with AD increases the chance of developing AD and that genetics was an important risk for AD. In addition, relative to White respondents, both Black and Latino respondents were more likely to perceive stress as a potential risk for AD. Latino respondents were less likely to perceive mental activity as a protective factor. CONCLUSIONS The study found limited ethnic group differences, with most items showing a similar pattern across groups. Nevertheless, the nature of the ethnic group differences found might be associated with a differential pattern of health service use.

False

CitationGPTRetr662

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Age-Related Chronic Diseases and Alzheimer's Disease in Texas: A Hispanic Focused Study. Abstract of the paper: The emergence of age-related chronic diseases within the United States has led to the direct increase of Alzheimer's disease (AD) as well as other neurological diseases which ultimately contribute to the development of dementia within the general population. To be specific, age-related chronic diseases such as cardiovascular disease, high cholesterol, diabetes, and kidney disease contribute greatly to the advancement and rapid progression of dementia. Furthermore, unmodifiable risk factors such as advancing age and genetics as well as modifiable risk factors such as socioeconomic status, educational attainment, exercise, and diet further contribute to the development of dementia. Current statistics and research show that minority populations such as Hispanic Americans in the United States face the greatest burden of dementia due to the increase in the prevalence of overall population age, predisposing genetics, age-related chronic diseases, low socioeconomic status, as well as poor lifestyle choices and habits. Additionally, Hispanic Americans living within Texas and the rural areas of West Texas face the added challenge of finding appropriate healthcare services. This article will focus upon the research associated with AD as well as the prevalence of AD within the Hispanic American population of Texas and rural West Texas. Furthermore, this article will also discuss the prevalence of age-related chronic diseases, unmodifiable risk factors, and modifiable risk factors which lead to the progression and development of AD within the Hispanic American population of the United States, Texas, and rural West Texas.

False

CitationGPTRetr663

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Abstract of the paper: Research on the relation between diabetes mellitus and dementia has produced conflicting results, and the relation has not been investigated among Blacks and Hispanics. In this study, Cox proportional hazards models were used to analyze longitudinal data from 1,262 elderly subjects without dementia at baseline (1991-1996) who were followed for an average of 4.3 years between 1992 and 1997. Outcomes were incident Alzheimer's disease and dementia associated with stroke. The prevalence of diabetes was 20% at baseline. The adjusted relative risk of Alzheimer's disease among persons with diabetes as compared with those without diabetes was 1.3 (95% confidence interval (CI): 0.8, 1.9). The adjusted relative risk for the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) in subjects with diabetes was 1.6 (95% CI: 1.2, 2.1). The adjusted relative risk of stroke-associated dementia in persons with diabetes was 3.4 (95% CI: 1.7, 6.9). Among Blacks and Hispanics, approximately one third of the risk of stroke-associated dementia was attributable to diabetes (33% (95% CI: 31, 36) and 36% (95% CI: 33, 37), respectively), as compared with 17% (95% CI: 13, 22) among Whites. The finding of an association between diabetes and the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) is consistent with prior reports of a modest relation between diabetes and Alzheimer's disease.

False

CitationGPTRetr664

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: The role of social and behavioral risk factors in explaining racial disparities in age-related cognitive impairment: a structured narrative review. Abstract of the paper: Alzheimer's disease (AD) is a growing public health concern with large disparities in incidence and prevalence between African Americans (AAs) and non-Hispanic whites (NHWs). The aim of this review was to examine the evidence of association between six modifiable risk factors (education, smoking, physical inactivity, obesity, social isolation, and psychosocial stress) and Alzheimer's disease risk in AAs and NHWs. We identified 3,437 studies; 45 met inclusion criteria and were included in this review. Of the examined risks, education provided the strongest evidence of association with cognitive outcomes in AAs and NHWs. This factor may operate directly on Alzheimer's disease risk through the neurocognitive benefits of cognitive stimulation or indirectly through social status.

False

CitationGPTRetr665

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Abstract of the paper: OBJECTIVE To compare the incidence rates for AD among elderly African-American, Caribbean Hispanic, and white individuals and to determine whether coincident cerebrovascular disease contributes to the inconsistency in reported differences among ethnic groups. METHODS This was a population-based, longitudinal study over a 7-year period in the Washington Heights and Inwood communities of New York City. Annual incidence rates for AD were calculated and compared by ethnic group, and cumulative incidence adjusted for differences in education, diabetes, cardiovascular risk factors, and stroke was calculated. RESULTS The age-specific incidence rate for probable and possible AD was 1.3% (95% CI, 0.8 to 1.7) per person-year between the ages of 65 and 74 years, 4.0% (95% CI, 3.2 to 4.8) per person-year between ages 75 and 84 years, and 7.9% (95% CI, 5.5 to 10.5) per person-year for ages 85 and older. Compared to white individuals, the cumulative incidence of AD to age 90 years was increased twofold among African-American and Caribbean Hispanic individuals. Adjustment for differences in number of years of education, illiteracy, or a history of stroke, hypertension, heart disease, or diabetes did not change the disproportionate risks among the three ethnic groups. CONCLUSION The incidence rate for AD was significantly higher among African-American and Caribbean Hispanic elderly individuals compared white individuals. The presence of clinically apparent cardiovascular or cerebrovascular disease did not contribute to the increased risk of disease. Because the proportion of African-American and Caribbean Hispanic individuals reaching ages 65 and older in the United States is increasing more rapidly than the proportion of white individuals, it is imperative that this disparity in health among the elderly be understood.

False

CitationGPTRetr666

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results. Abstract of the paper: INTRODUCTION We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos. METHODS Middle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria. RESULTS The overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI. DISCUSSION MCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.

False

CitationGPTRetr667

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Public opinion about Alzheimer disease among blacks, hispanics, and whites: results from a national survey. Abstract of the paper: Recent research has documented notable differences in knowledge, awareness, and cultural beliefs about Alzheimer disease (AD) among groups defined by race and ethnicity. The present study was conducted to assess racial differences in knowledge and attitudes about AD among a national sample of adults. Data from 1,176 adults aged 35 years and over (48.6% White, 25.7% Black, and 25.8% Hispanic) obtained via telephone interview were used in this study. Although some notable group differences defined by race/ethnicity were observed, more similarities in patterns of response were discovered than expected. Black and Hispanic respondents were significantly more likely to believe that AD is a normal part of aging, but were more optimistic about future advances in research than White participants. Compared with White and Black respondents, Hispanics were more likely to report feeling well-prepared for handling a diagnosis of AD in a family member. Overall, the results suggest that misconceptions about AD remain among large segments of the population, that AD remains a source of significant concern, and that continued efforts are needed to educate the public about this disease.

False

CitationGPTRetr668

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Racial and ethnic differences in trends in dementia prevalence and risk factors in the United States. Abstract of the paper: INTRODUCTION Disparities in dementia prevalence across racial/ethnic groups in the United States may not be narrowing over time. METHODS Data from Health and Retirement Study (2000 to 2012) were analyzed. Dementia was ascertained based on cognitive, functional measures. Logistic regression was used to quantify association between dementia and risk factors, including chronic conditions, use of drug treatment for them, separately for whites, blacks, and Hispanics. RESULTS Disparities in dementia prevalence declined between blacks and whites and increased between Hispanics and whites. Adjusting for risk factors reduced but did not eliminate disparities. Compared to no hypertension, untreated hypertension was associated with increased risk of dementia for all racial/ethnic groups while treated hypertension was associated with reduced risk for whites. Diabetes treated with oral drugs was not associated with increased dementia risk. DISCUSSION Racial disparities in dementia may be reduced by prevention and management of disease and promoting educational attainment among blacks and Hispanics.

False

CitationGPTRetr669

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Alzheimer's disease in African Americans: risk factors and challenges for the future. Abstract of the paper: As the US elderly population continues to expand rapidly, Alzheimer's disease poses a major and increasing public health challenge, and older African Americans may be disproportionately burdened by the disease. Although African Americans were generally underincluded in previous research studies, new and growing evidence suggests that they may be at increased risk of the disease and that they differ from the non-Hispanic white population in risk factors and disease manifestation. This article offers an overview of the challenges of Alzheimer's disease in African Americans, including diagnosis issues, disparities in risk factors and clinical presentation of disease, and community-based recommendations to enhance research with this population.

False

CitationGPTRetr670

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Health Disparities in Dementia. Abstract of the paper: PURPOSE OF REVIEW Causes of health disparities in Alzheimer disease and related dementias (ADRD) in the United States are multifactorial. This article contextualizes health disparities as they relate to the neurodegenerative processes of ADRD. RECENT FINDINGS Older adults' life expectancy has increased such that a 65-year-old is expected to live 19 or more years and an 85-year-old can expect to live, on average, 6 to 7 years longer. Individuals of certain ethnoracial groups (Black, Hispanic/Latino, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) may be at a higher risk of incident ADRD compared to non-Hispanic/Latino White people. These differences in a higher risk of ADRD across ethnoracial groups persist despite no statistically significant differences in the rate of cognitive decline over time. The intersectionality of social determinants of health, experiences with discrimination and oppression, and access to care are related to the issue of justice and the risk for and expression of ADRD. The theoretical frameworks of various health disparities provide organized approaches to tracking the progression of health disparities for diverse patients. SUMMARY ADRD health disparities are complex. Neurologists and their care teams must consider the main reasons for clinical ADRD evaluations of members of ethnoracial groups and the factors that may impact patient adherence and compliance with diagnostic and management recommendations.

False

CitationGPTRetr671

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: A research framework for cognitive aging and Alzheimer's disease among diverse US Latinos: Design and implementation of the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). Abstract of the paper: Hispanics/Latinos are the largest ethnic/racial group in the United States and at high risk for Alzheimer's disease and related dementia (ADRD). Yet, ADRD among diverse Latinos is poorly understood and disparately understudied or unstudied compared to other ethnic/racial groups that leave the nation ill-prepared for major demographic shifts that lay ahead in coming decades. The primary purpose of this Perspectives article was to provide a new research framework for advancing Latino ADRD knowledge, encompassing the unique sociocultural, cardiometabolic, and genomic aspects of Latino health, aging, and ADRD. In addition, we describe some of the research challenges to progress in Latino ADRD research. Finally, we present the Study of Latinos - Investigation of Neurocognitive Aging (SOL-INCA) as an example of implementing this new framework for advancing Latino ADRD research.

False

CitationGPTRetr672

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the second Latinos & Alzheimer's Symposium. Abstract of the paper: The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD.

False

CitationGPTRetr673

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Metabolic Factors Are Related to Brain Amyloid Among Mexican Americans: A HABS-HD Study. Abstract of the paper: BACKGROUND Despite the tremendous amount of research on Alzheimer's disease (AD) biomarkers, very little data is available regarding the fundamental biomarkers of AD among Mexican Americans. OBJECTIVE Here we sought to examine the link between metabolic markers and brain amyloid among Mexican Americans as compared to non-Hispanic whites from the Health & Aging Brain Study -Health Disparities (HABS-HD) cohort. METHODS PET amyloid (florbetaben) data was analyzed from 34 Mexican American and 22 non-Hispanic white participants. RESULTS Glucagon (t = 3.84, p < 0.001) and insulin (t = -2.56, p = 0.02) were both significantly related to global SUVR levels among Mexican Americans. Glucagon and insulin were both related to most ROIs. No metabolic markers were significantly related to brain amyloid levels among non-Hispanic whites. CONCLUSION Metabolic markers are related to brain amyloid burden among Mexican Americans. Given the increased risk for diabetes, additional research is needed to determine the impact of diabetes on core AD biomarkers among this underserved population.

False

CitationGPTRetr674

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Racial and Ethnic Disparities in Serious Psychological Distress Among Those With Alzheimer's Disease and Related Dementias. Abstract of the paper: BACKGROUND Alzheimer's disease and related dementias (ADRD) is a growing public health challenge. Prior research suggests that non-Hispanic whites (whites), non-Hispanic African Americans (African Americans), and Hispanics have differing risks for ADRD. OBJECTIVE To examine the existence of serious psychological distress (SPD) among whites, African Americans, and Hispanics; to calculate the predicted probability of ADRD in whites, African Americans, and Hispanics, and to decompose the differences among ADRD populations, quantifying the burden of higher SPD among African Americans and Hispanics, compared to whites. DATA AND METHOD The authors use nationally representative data from the Medical Expenditure Panel Survey (2007-2015) to estimate the association between ADRD and race, ethnicity, and SPD. Using Blinder-Oaxaca decomposition analysis, the authors estimate to what extent higher SPD among Hispanics and African Americans was associated with higher ADRD rates compared to whites. RESULTS After controlling for individuals' demographic and socioeconomic characteristics and co-existing medical conditions, the presence of SPD was still significantly associated with a higher likelihood of having ADRD. The model predicted significantly higher likelihood of having ADRD among African Americans (7.1%) and Hispanics (5.7%) compared to whites (4.5%). Higher rates of having SPD among African Americans explained 15% of white-black difference and 40% of the white-Hispanic difference in ADRD rates, respectively. DISCUSSION AND CONCLUSION Our findings suggest a significant relationship between SPD and ADRD and that the burden of SPD was greater among African Americans and Hispanics with ADRD. Efficient screening using self-reported SPD, compared to simply using diagnoses codes of mental illness, may be more helpful to reduce racial and ethnic disparities in ADRD.

False

CitationGPTRetr675

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Global epidemiology of dementia: Alzheimer's and vascular types. Abstract of the paper: The prevalence of dementia varies substantially worldwide. This is partially attributed to the lack of methodological uniformity among studies, including diagnostic criteria and different mean population ages. However, even after considering these potential sources of bias, differences in age-adjusted dementia prevalence still exist among regions of the world. In Latin America, the prevalence of dementia is higher than expected for its level of population aging. This phenomenon occurs due to the combination of low average educational attainment and high vascular risk profile. Among developed countries, Japan seems to have the lowest prevalence of dementia. Studies that evaluated the immigration effect of the Japanese and blacks to USA evidenced that acculturation increases the relative proportion of AD cases compared to VaD. In the Middle East and Africa, the number of dementia cases will be expressive by 2040. In general, low educational background and other socioeconomic factors have been associated with high risk of obesity, sedentarism, diabetes, hypertension, dyslipidemia, and metabolic syndrome, all of which also raise the risk of VaD and AD. Regulating these factors is critical to generate the commitment to make dementia a public health priority.

False

CitationGPTRetr676

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Racial/ethnic differences in dementia risk among older type 2 diabetic patients: the diabetes and aging study. Abstract of the paper: OBJECTIVE Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients. RESEARCH DESIGN AND METHODS We identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control. RESULTS Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30-2.06) for Native Americans, 1.44 (1.24-1.67) for African Americans, 1.30 (1.15-1.47) for non-Hispanic whites, and 1.19 (1.02-1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results. CONCLUSIONS Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40-60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.

False

CitationGPTRetr677

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: The projected effect of risk factor reduction on Alzheimer's disease prevalence. Abstract of the paper: At present, about 33·9 million people worldwide have Alzheimer's disease (AD), and prevalence is expected to triple over the next 40 years. The aim of this Review was to summarise the evidence regarding seven potentially modifiable risk factors for AD: diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity. Additionally, we projected the effect of risk factor reduction on AD prevalence by calculating population attributable risks (the percent of cases attributable to a given factor) and the number of AD cases that might be prevented by risk factor reductions of 10% and 25% worldwide and in the USA. Together, up to half of AD cases worldwide (17·2 million) and in the USA (2·9 million) are potentially attributable to these factors. A 10-25% reduction in all seven risk factors could potentially prevent as many as 1·1-3·0 million AD cases worldwide and 184,000-492,000 cases in the USA.

False

CitationGPTRetr678

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Dementia Prevalence in Older Adults: Variation by Race/Ethnicity and Immigrant Status. Abstract of the paper: OBJECTIVE To examine differences in prevalence and risk factors of dementia by race/ethnicity and immigrant status using a nationally representative sample of Medicare beneficiaries. METHODS This was a cross-sectional study performed in the United States among non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and other Medicare beneficiaries from round 1 of the National Health and Aging Trends Study (N = 7,609). The authors used log-binomial regression analyses to investigate risk factors and interactions between race/ethnicity and immigrant status and dementia. Stratified log-binomial regression analyses by race/ethnicity were used to interpret the results of interaction effects of immigrant status found in these surveys. Analyses were conducted in three forms: probable dementia versus possible and no dementia, probable and possible dementia versus no dementia; and probable dementia versus no dementia. RESULTS Consistent with previous studies, U.S.-born NHBs have a higher prevalence of dementia than U.S.-born whites, Hispanics, and others. Immigrant status moderated the relationship between race/ethnicity and dementia. NHWs, Hispanics, and other immigrants had a higher prevalence of dementia compared with their U.S.-born counterparts. However, U.S.-born NHBs had a higher prevalence of dementia compared with NHB immigrants. Results were consistent across the three forms of analysis. Greater age predicted higher dementia across the four racial/ethnic groups. CONCLUSION Immigrant status may have complex effects on dementia risk. Selection factors affecting immigration-varied health and educational systems in diverse countries of origin, acculturative stress, and validity of dementia assessment across diverse groups-deserve further attention.

False

CitationGPTRetr679

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: ad disproportionately affects hispanicslatinos compared to nhws eg one study indicates 14 of aging hispanics have ad compared to 10 of aging nhws and others report that aging hispanics are about 15 times as likely to have ad compared to aging nhws this is thought to be due to the increased prevalence of metabolic syndrome obesity cardiovascular health risks and diabetes Title of the paper: Alzheimer's Disease and Alzheimer's Disease-Related Dementias in African Americans: Focus on Caregivers. Abstract of the paper: Alzheimer's disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) are chronic illnesses that are highly prevalent in African Americans (AA). AD and ADRD are caused by multiple factors, such as genetic mutations, modifiable and non-modifiable risk factors, and lifestyle. Histopathological, morphological, and cellular studies revealed how multiple cellular changes are implicated in AD and ADRD, including synaptic damage, inflammatory responses, hormonal imbalance, mitochondrial abnormalities, and neuronal loss, in addition to the accumulation of amyloid beta and phosphorylated tau in the brain. The contributions of race, ethnicity, location and socioeconomic status all have a significant impact on the care and support services available to dementia patients. Furthermore, disparities in health care are entangled with social, economic, and environmental variables that perpetuate disadvantages among different groups, particularly African Americans. As such, it remains important to understand how various racial and ethnic groups perceive, access, and experience health care. Considering that the mounting data shows AA may be more susceptible to AD than white people, the demographic transition creates significant hurdles in providing adequate care from family caregivers. Furthermore, there is growing recognition that AD and ADRD pose a significant stress on AA caregivers compared to white people. In this review, we examine the current literature on racial disparities in AD and ADRD, particularly concerning AA caregivers.

False

CitationGPTRetr680

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Epigenetic nutraceutical diets in Alzheimer's disease. Abstract of the paper: There is growing support that environmental influences and individual genetic susceptibility may increase the incidence and accelerate the onset of Alzheimer's disease (AD). Epigenetic mechanisms encompass a complex regulatory network of modifications with considerable impact on health and disease risk. Abnormal epigenetic regulation is a hallmark in many pathological conditions including AD. It is well recognized that numerous bioactive dietary components mediate epigenetic modifications associated with the pathophysiology of several diseases. Although the influences of dietary factors on epigenetic regulation have been extensively investigated, only few studies have explored the effects of specific food components in regulating epigenetic patterns during neurodegeneration and AD. Epigenetic nutritional research has substantial potential for AD and may represent a window of opportunity to complement other interventions. Here, we provide a brief overview of the main mechanisms involved in AD, some of which may be epigenetically modulated by bioactive food.

False

CitationGPTRetr681

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Nutritional influences on epigenetics and age-related disease. Abstract of the paper: Nutritional epigenetics has emerged as a novel mechanism underlying gene-diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern.

False

CitationGPTRetr682

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Alzheimer's disease and epigenetic diet. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disease. Many efforts have been directed to prevent AD due to its rising prevalence and the lack of an effective curative treatment. Various epigenetic mechanisms are linked to pathogenesis of AD. Epigenetic alterations may occur through external factors and are known for their reversibility. Dietary factors can influence epigenetic mechanisms. Several neuroprotective nutrients have been shown to enhance cognition, memory and other impaired functions seen in AD. Within recent years neuroprotective nutrients have gained more attention in the field of epigenetic. A growing body of evidence suggest that epigenetic changes triggered by dietary nutrients have an important role in health and in prevention of some diseases, especially neurodegenerative disorders. Several studies have shown that folic acid, vitamin B12, choline, zinc, selenium, dietary polyphenols are capable of interacting with epigenetic mechanisms and ultimately gene expression. Epigenetic mechanisms resulting in neuronal dysfunction may be modified by diet. Therefore manipulation of epigenetic mechanisms via dietary nutrients may affect influence the vulnerability of neurons to degeneration which is seen in AD. The aim of this article is to provide a brief overview about the recent findings related to epigenetic alterations that are linked to AD pathogenesis, and to discuss the bioactive nutrients which can affect these epigenetic mechanisms.

False

CitationGPTRetr683

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Environment, epigenetics and neurodegeneration: Focus on nutrition in Alzheimer's disease. Abstract of the paper: Many different environmental factors (nutrients, pollutants, chemicals, physical activity, lifestyle, physical and mental stress) can modulate epigenetic markers in the developing and adult organism. Epigenetics, in turn, can cause and is associated with several neurodegenerative and aging-dependent human diseases. Alzheimer's disease certainly represents one of the most relevant neurodegenerative disorders due to its incidence and its huge socio-economic impact. Therefore, it is easy to understand why recent literature focuses on the epigenetic modifications associated with Alzheimer's disease and other neurodegenerative disorders. One of the most intriguing and, at the same time, worrying evidence is that even "mild" environmental factors (such as behavioral or physical stress) as well as the under-threshold exposure to pollutants and chemicals, can be effective. Finally, even mild nutrients disequilibria can result in long-lasting and functional alterations of many epigenetic markers, although they don't have an immediate acute effect. Therefore, we will probably have to re-define the current risk threshold for many factors, molecules and stresses. Among the many different environmental factors affecting the epigenome, nutrition represents one of the most investigated fields; the reasons are probably that each person interacts with nutrients and that, in turn, nutrients can modulate at molecular level the epigenetic biochemical pathways. The role that nutrition can exert in modulating epigenetic modifications in Alzheimer's disease will be discussed with particular emphasis on the role of B vitamins and DNA methylation.

False

CitationGPTRetr684

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Nutrition, the brain and cognitive decline: insights from epigenetics. Abstract of the paper: Nutrition affects the brain throughout life, with profound implications for cognitive decline and dementia. These effects are mediated by changes in expression of multiple genes, and responses to nutrition are in turn affected by individual genetic variability. An important layer of regulation is provided by the epigenome: nutrition is one of the many epigenetic regulators that modify gene expression without changes in DNA sequence. Epigenetic mechanisms are central to brain development, structure and function, and include DNA methylation, histone modifications and non-protein-coding RNAs. They enable cell-specific and age-related gene expression. Although epigenetic events can be highly stable, they can also be reversible, highlighting a critical role for nutrition in prevention and treatment of disease. Moreover, they suggest key mechanisms by which nutrition is involved in the pathogenesis of age-related cognitive decline: many nutrients, foods and diets have both immediate and long-term effects on the epigenome, including energy status, that is, energy intake, physical activity, energy metabolism and related changes in body composition, and micronutrients involved in DNA methylation, for example, folate, vitamins B6 and B12, choline, methionine. Optimal brain function results from highly complex interactions between numerous genetic and environmental factors, including food intake, physical activity, age and stress. Future studies linking nutrition with advances in neuroscience, genomics and epigenomics should provide novel approaches to the prevention of cognitive decline, and treatment of dementia and Alzheimer's disease.

False

CitationGPTRetr685

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Role of methionine on epigenetic modification of DNA methylation and gene expression in animals. Abstract of the paper: DNA methylation is one of the main epigenetic phenomena affecting gene expression. It is an important mechanism for the development of embryo, growth and health of animals. As a key nutritional factor limiting the synthesis of protein, methionine serves as the precursor of S-adenosylmethionine (SAM) in the hepatic one-carbon metabolism. The dietary fluctuation of methionine content can alter the levels of metabolic substrates in one-carbon metabolism, e.g., the SAM, S-adenosylhomocysteine (SAH), and change the expression of genes related to the growth and health of animals by DNA methylation reactions. The ratio of SAM to SAH is called 'methylation index' but it should be carefully explained because the complexity of methylation reaction. Alterations of methylation in a specific cytosine-guanine (CpG) site, rather than the whole promoter region, might be enough to change gene expression. Aberrant methionine cycle may provoke molecular changes of one-carbon metabolism that results in deregulation of cellular hemostasis and health problems. The importance of DNA methylation has been underscored but the mechanisms of methionine affecting DNA methylation are poorly understood. Nutritional epigenomics provides a promising insight into the targeting epigenetic changes in animals from a nutritional standpoint, which will deepen and expand our understanding of genes, molecules, tissues, and animals in which methionine alteration influences DNA methylation and gene expression.

False

CitationGPTRetr686

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Nutri-epigenetics ameliorates blood-brain barrier damage and neurodegeneration in hyperhomocysteinemia: role of folic acid. Abstract of the paper: Epigenetic mechanisms underlying nutrition (nutrition epigenetics) are important in understanding human health. Nutritional supplements, for example folic acid, a cofactor in one-carbon metabolism, regulate epigenetic alterations and may play an important role in the maintenance of neuronal integrity. Folic acid also ameliorates hyperhomocysteinemia, which is a consequence of elevated levels of homocysteine. Hyperhomocysteinemia induces oxidative stress that may epigenetically mediate cerebrovascular remodeling and leads to neurodegeneration; however, the mechanisms behind such alterations remain unclear. Therefore, the present study was designed to observe the protective effects of folic acid against hyperhomocysteinemia-induced epigenetic and molecular alterations leading to neurotoxic cascades. To test this hypothesis, we employed 8-weeks-old male wild-type (WT) cystathionine-beta-synthase heterozygote knockout methionine-fed (CBS+/− + Met), WT, and CBS+/− + Met mice supplemented with folic acid (FA) [WT + FA and CBS+/− + Met + FA, respectively, 0.0057-μg g−1 day−1 dose in drinking water/4 weeks]. Hyperhomocysteinemia in CBS+/− + Met mouse brain was accompanied by a decrease in methylenetetrahydrofolate reductase and an increase in S-adenosylhomocysteine hydrolase expression, symptoms of oxidative stress, upregulation of DNA methyltransferases, rise in matrix metalloproteinases, a drop in the tissue inhibitors of metalloproteinases, decreased expression of tight junction proteins, increased permeability of the blood-brain barrier, neurodegeneration, and synaptotoxicity. Supplementation of folic acid to CBS+/− + Met mouse brain led to a decrease in the homocysteine level and rescued pathogenic and epigenetic alterations, showing its protective efficacy against homocysteine-induced neurotoxicity.

False

CitationGPTRetr687

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: The 'golden age' of DNA methylation in neurodegenerative diseases. Abstract of the paper: DNA methylation reactions are regulated, in the first instance, by enzymes and the intermediates that constitute the 'so called' one-carbon metabolism. This is a complex biochemical pathway, also known as the homocysteine cycle, regulated by the presence of B vitamins (folate, B6, B12) and choline, among other metabolites. One of the intermediates of this metabolism is S-adenosylmethionine, which represent the methyl donor in all the DNA methyltransferase reactions in eukaryotes. The one-carbon metabolism therefore produces the substrate necessary for the transferring of a methyl group on the cytosine residues of DNA; S-adenosylmethionine also regulates the activity of the enzymes that catalyze this reaction, namely the DNA methyltransferases (DNMTs). Alterations of this metabolic cycle can therefore be responsible for aberrant DNA methylation processes possibly leading to several human diseases. As a matter of fact, increasing evidences indicate that a number of human diseases with multifactorial origin may have an epigenetic basis. This is also due to the great technical advances in the field of epigenetic research. Among the human diseases associated with epigenetic factors, aging-related and neurodegenerative diseases are probably the object of most intense research. This review will present the main evidences linking several human diseases to DNA methylation, with particular focus on neurodegenerative diseases, together with a short description of the state-of-the-art of methylation assays.

False

CitationGPTRetr688

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Nutriepigenetics and cardiovascular disease. Abstract of the paper: PURPOSE OF REVIEW We present a current perspective of epigenetic alterations that can lead to cardiovascular disease (CVD) and the potential of dietary factors to counteract their actions. In addition, we discuss the challenges and opportunities of dietary treatments as epigenetic modifiers for disease prevention and therapy. RECENT FINDINGS Recent epigenome-wide association studies along with candidate gene approaches and functional studies in cell culture and animal models have delineated mechanisms through which nutrients, food compounds and dietary patterns may affect the epigenome. Several risk factors for CVD, including adiposity, inflammation and oxidative stress, have been associated with changes in histone acetylation, lower global DNA methylation levels and shorter telomere length. A surplus of macronutrients such as in a high-fat diet or deficiencies of specific nutrients such as folate and other B-vitamins can affect the activity of DNA methyltransferases and histone-modifying enzymes, affecting foetal growth, glucose/lipid metabolism, oxidative stress, inflammation and atherosclerosis. Bioactive compounds such as polyphenols (resveratrol, curcumin) or epigallocatechin may activate deacetylases Sirtuins (SIRTs), histone deacetylases or acetyltransferases and in turn the response of inflammatory mediators. Adherence to cardioprotective dietary patterns, such as the Mediterranean diet (MedDiet), has been associated with altered methylation and expression of genes related to inflammation and immuno-competence. SUMMARY The mechanisms through which nutrients and dietary patterns may alter the cardiovascular epigenome remain elusive. The research challenge is to determine which of these nutriepigenetic effects are reversible, so that novel findings translate into effective dietary interventions to prevent CVD or its progression.

False

CitationGPTRetr689

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: One-carbon metabolism and Alzheimer's disease: is it all a methylation matter? Abstract of the paper: The sporadic form of Alzheimer disease, late onset Alzheimer's disease (LOAD), is a multifactorial disease; a strong link between nutritional and genetic factors with normal aging and dementia is supported by studies on nutrition, metabolism, and neurodegeneration. Specifically, the involvement of homocysteine (HCY) and its dietary determinants (vitamins B6, B12, and folate, besides methionine) in dementia has been a topic of intense investigation. In this Commentary we would like to highlight the role of 1-carbon metabolism in epigenetics and Alzheimer's disease and evidence the co-involvement of this metabolism in amyloid and tau pathways.

False

CitationGPTRetr690

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Diet induced epigenetic changes and their implications for health. Abstract of the paper: Dietary exposures can have consequences for health years or decades later and this raises questions about the mechanisms through which such exposures are 'remembered' and how they result in altered disease risk. There is growing evidence that epigenetic mechanisms may mediate the effects of nutrition and may be causal for the development of common complex (or chronic) diseases. Epigenetics encompasses changes to marks on the genome (and associated cellular machinery) that are copied from one cell generation to the next, which may alter gene expression, but which do not involve changes in the primary DNA sequence. These include three distinct, but closely inter-acting, mechanisms including DNA methylation, histone modifications and non-coding microRNAs (miRNA) which, together, are responsible for regulating gene expression not only during cellular differentiation in embryonic and foetal development but also throughout the life-course. This review summarizes the growing evidence that numerous dietary factors, including micronutrients and non-nutrient dietary components such as genistein and polyphenols, can modify epigenetic marks. In some cases, for example, effects of altered dietary supply of methyl donors on DNA methylation, there are plausible explanations for the observed epigenetic changes, but to a large extent, the mechanisms responsible for diet-epigenome-health relationships remain to be discovered. In addition, relatively little is known about which epigenomic marks are most labile in response to dietary exposures. Given the plasticity of epigenetic marks and their responsiveness to dietary factors, there is potential for the development of epigenetic marks as biomarkers of health for use in intervention studies.

False

CitationGPTRetr691

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Abstract of the paper: Nutrition exerts considerable effects on health, and dietary interventions are commonly used to treat diseases of metabolic aetiology. Although cancer has a substantial metabolic component1, the principles that define whether nutrition may be used to influence outcomes of cancer are unclear2. Nevertheless, it is established that targeting metabolic pathways with pharmacological agents or radiation can sometimes lead to controlled therapeutic outcomes. By contrast, whether specific dietary interventions can influence the metabolic pathways that are targeted in standard cancer therapies is not known. Here we show that dietary restriction of the essential amino acid methionine-the reduction of which has anti-ageing and anti-obesogenic properties-influences cancer outcome, through controlled and reproducible changes to one-carbon metabolism. This pathway metabolizes methionine and is the target of a variety of cancer interventions that involve chemotherapy and radiation. Methionine restriction produced therapeutic responses in two patient-derived xenograft models of chemotherapy-resistant RAS-driven colorectal cancer, and in a mouse model of autochthonous soft-tissue sarcoma driven by a G12D mutation in KRAS and knockout of p53 (KrasG12D/+;Trp53-/-) that is resistant to radiation. Metabolomics revealed that the therapeutic mechanisms operate via tumour-cell-autonomous effects on flux through one-carbon metabolism that affects redox and nucleotide metabolism-and thus interact with the antimetabolite or radiation intervention. In a controlled and tolerated feeding study in humans, methionine restriction resulted in effects on systemic metabolism that were similar to those obtained in mice. These findings provide evidence that a targeted dietary manipulation can specifically affect tumour-cell metabolism to mediate broad aspects of cancer outcome.

False

CitationGPTRetr692

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Longevity: epigenetic and biomolecular aspects. Abstract of the paper: Many aging theories and their related molecular mechanisms have been proposed. Simple model organisms such as yeasts, worms, fruit flies and others have massively contributed to their clarification, and many genes and pathways have been associated with longevity regulation. Among them, insulin/IGF-1 plays a key and evolutionary conserved role. Interestingly, dietary interventions can modulate this pathway. Calorie restriction (CR), intermittent fasting, and protein and amino acid restriction prolong the lifespan of mammals by IGF-1 regulation. However, some recent findings support the hypothesis that the long-term effects of diet also involve epigenetic mechanisms. In this review, we describe the best characterized aging pathways and highlight the role of epigenetics in diet-mediated longevity.

False

CitationGPTRetr693

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models. Abstract of the paper: Late-onset Alzheimer's disease seems to be a multi-factorial disease with both genetic and non-genetic, environmental, possible causes. Recently, epigenomics is achieving a major role in Alzheimer's research due to its involvement in different molecular pathways leading to neurodegeneration. Among the different epigenetic modifications, DNA methylation is one of the most relevant to the disease. We previously demonstrated that presenilin1 (PSEN1), a gene involved in amyloidogenesis, is modulated by DNA methylation in neuroblastoma cells and Alzheimer's mice in an experimental model of nutritionally altered one-carbon metabolism. This alteration, obtained by nutritional deficiency of B vitamins (folate, B12 and B6) hampered S-adenosylmethionine (SAM)-dependent methylation reactions. The aim of the present paper was to investigate the regulation of DNA methylation machinery in response to hypomethylating (B vitamin deficiency) and hypermethylating (SAM supplementation) alterations of the one-carbon metabolism. We found that DNA methylases (DNMT1, 3a and 3b) and a putative demethylase (MBD2) were differently modulated, in line with the previously observed changes of PSEN1 methylation pattern in the same experimental conditions.

False

CitationGPTRetr694

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Effects of methionine intake on cognitive function in mild cognitive impairment patients and APP/PS1 Alzheimer's Disease model mice: Role of the cystathionine-β-synthase/H2S pathway. Abstract of the paper: As a dietary intervention, methionine restriction (MR) has been reported to increase longevity and improve metabolism disorders. However, the effects of MR on alleviating neurodegenerative diseases such as Alzheimer's disease (AD) are largely unexplored. Here we sought to investigate the neuroprotective effects of low methionine intake in mild cognitive impairment (MCI) patients and APP/PS1 AD model mice, and to uncover the underlying mechanisms. In a cohort composed of 45 individuals diagnosed with MCI and 61 healthy controls without cognitive impairment, methionine intake was found to be positively associated with the increased risk of MCI, where no sex differences were observed. We further conducted a 16-week MR intervention (0.17% methionine, w/w) on APP/PS1 AD model mice. Although MR reduced Aβ accumulation in the brain of both male and female APP/PS1 mice, MR improved cognitive function only in male mice, as assessed by the Morris water maze test. Consistently, MR restored synapse ultrastructure and alleviated mitochondrial dysfunction by enhancing mitochondrial biogenesis in the brain of male APP/PS1 mice. Importantly, MR effectively balanced the redox status and activated cystathionine-β-synthase (CBS)/H2S pathway in the brain of male APP/PS1 mice. Together, our study indicated that lower dietary methionine intake is associated with improved cognitive function, in which CBS/H2S pathway plays an essential role. MR could be a promising nutritional intervention for preventing AD development.

False

CitationGPTRetr695

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Abstract of the paper: Folate is a cofactor in one-carbon metabolism, during which it promotes the remethylation of homocysteine -- a cytotoxic sulfur-containing amino acid that can induce DNA strand breakage, oxidative stress and apoptosis. Dietary folate is required for normal development of the nervous system, playing important roles regulating neurogenesis and programmed cell death. Recent epidemiological and experimental studies have linked folate deficiency and resultant increased homocysteine levels with several neurodegenerative conditions, including stroke, Alzheimer's disease and Parkinson's disease. Moreover, genetic and clinical data suggest roles for folate and homocysteine in the pathogenesis of psychiatric disorders. A better understanding of the roles of folate and homocysteine in neuronal homeostasis throughout life is revealing novel approaches for preventing and treating neurological disorders.

False

CitationGPTRetr696

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: L-methionine enhances neuroinflammation and impairs neurogenesis: Implication for Alzheimer's disease. Abstract of the paper: The disruption of methionine (L-MET) metabolism has been linked with neurodevelopmental disorders such as autism and schizophrenia and neurodegenerative disorders such as Alzheimer's disorder. We previously showed that repeated administration to adult mice of methionine produced impairments of cognitive deficits. Considering the decreased neurogenesis and increased molecular inflammation hypotheses of cognitive deficits in Alzheimer's, we aimed to explore whether the methionine regimen that produced cognitive deficits is associated with altered neuroinflammation, neurogenesis, or neurodegeneration. We found that repeated administration of L-MET at a dose equivalent to two-fold of daily dietary intake for seven days enhanced the activation of microglia and inflammation in the brain, and decreased neurogenesis in the hippocampus without affecting degeneration. Furthermore, sub-chronic and chronic L-MET treatment of human neuroblastoma (SH-SY5Y) inhibited cell cycle progression, an effect that was reversed by decreasing removing L-MET from the medium. These results support a role for neuroinflammation and neurogenesis in mediating the mechanism through which L-MET induces cognitive deficits. The results also uncover L-MET restriction, neuroinflammation, and neurogenesis as potential preventive and/or therapeutic targets for mental disorders associated with cognitive disorders, including schizophrenia and Alzheimer's disease.

False

CitationGPTRetr697

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Early Life Nutrition and Mental Health: The Role of DNA Methylation. Abstract of the paper: Does the quality of our diet during early life impact our long-term mental health? Accumulating evidence suggests that nutrition interacts with our genes and that there is a strong association between the quality of diet and mental health throughout life. Environmental influences such as maternal diet during pregnancy or offspring diet have been shown to cause epigenetic changes during critical periods of development, such as chemical modifications of DNA or histones by methylation for the regulation of gene expression. One-carbon metabolism, which consists of the folate and methionine cycles, is influenced by the diet and generates S-Adenosylmethinoine (SAM), the main methyl donor for methylation reactions such as DNA and histone methylation. This review provides current knowledge on how the levels of one-carbon metabolism associated micronutrients such as choline, betaine, folate, methionine and B vitamins that play a role in brain function can impact our well-being and mental health across the lifespan. Micronutrients that act as methyl donors for SAM formation could affect global or gene methylation, altering gene expression and phenotype. Strategies should then be adopted to better understand how these nutrients work and their impact at different stages of development to provide individualized dietary recommendations for better mental health outcomes.

False

CitationGPTRetr698

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: S-adenosyl methionine: A connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer's disease. Abstract of the paper: Clinical manifestation of Alzheimer's disease may depend upon interaction among its risk factors. Apolipoprotein E-deficient mice undergo oxidative damage and cognitive impairment when deprived of folate. We demonstrate herein that these mice were depleted in the methyl donor S-adenosyl methionine (SAM), which inhibited glutathione S-transferase, since this enzyme requires methylation of oxidative species prior to glutathione-dependent reduction. Dietary supplementation with SAM alleviated neuropathology. Since SAM deficiency promotes presenilin-1 overexpression, which increases gamma-secretase expression and Abeta generation, these findings directly link nutritional deficiency and genetic risk factors, and support supplementation with SAM for Alzheimer's therapy.

False

CitationGPTRetr699

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: with the development of nutritional epigenetics nutraceuticals and dietary interventions 568 it has been established that the disruption of methionine met metabolism significantly contributes to the development and progression of neurodegenerative diseases Title of the paper: Metaboloepigenetics: interrelationships between energy metabolism and epigenetic control of gene expression. Abstract of the paper: Diet and energy metabolism affect gene expression, which influences human health and disease. Here, we discuss the role of epigenetics as a mechanistic link between energy metabolism and control of gene expression. A number of key energy metabolites including SAM, acetyl-CoA, NAD(+), and ATP serve as essential co-factors for many, perhaps most, epigenetic enzymes that regulate DNA methylation, posttranslational histone modifications, and nucleosome position. The relative abundance of these energy metabolites allows a cell to sense its energetic state. And as co-factors, energy metabolites act as rheostats to modulate the activity of epigenetic enzymes and upregulate/downregulate transcription as appropriate to maintain homeostasis.

False