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CitationGPTv2_test

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CitationGPTRetr11200

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Metabolic syndrome and cognitive disorders: is the sum greater than its parts? Abstract of the paper: Given the anticipated exponential increase in both the incidence and prevalence of dementia, it is critical to identify preventative strategies and improved treatments for this disorder. The metabolic syndrome is comprised of 5 cardiovascular risk factors that include abdominal obesity, hypertriglyceridemia, low high-density lipoprotein levels, hypertension, and hyperglycemia. The prevalence of the metabolic syndrome, similar to that for cognitive disorders, increases dramatically with age. Several possible mechanisms may explain an association between the metabolic syndrome and cognitive decline including microvascular and macrovascular disease, inflammation, adiposity, and insulin resistance. Although some of the individual components of the metabolic syndrome have been linked to risk of developing dementia and cognitive impairment, few studies have looked at the components of the metabolic syndrome as a whole. We found, in 3 separate studies involving elders of different ethnicities, that the metabolic syndrome is a risk factor for accelerated cognitive aging. This was especially true for elders with the metabolic syndrome and with elevated serum level of inflammation. If metabolic syndrome is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals might offer avenues for disease course modification.

False

CitationGPTRetr11201

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular risk factors and Alzheimer's disease. Abstract of the paper: Alzheimer's disease is a devastating condition that is increasing in prevalence. No known prevention or cure exists for Alzheimer's disease. Cardiovascular risk factors are prevalent and increase in the elderly, and there have been conflicting reports of associations between modifiable cardiovascular risk factors and Alzheimer's disease. The mechanisms for these associations are uncertain, but they are likely to be the result of a combination of direct and cerebrovascular disease-related mechanisms. From this standpoint, diabetes and hyperinsulinemia seem to have the strongest evidence from laboratory, clinical, and epidemiologic studies. Studies have also indicated that hypertension, hyperlipidemia, hyperhomocysteinemia, and smoking are potentially important risk factors for Alzheimer's disease.

False

CitationGPTRetr11202

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: The complex interplay of cardiovascular system and cognition: how to predict dementia in the elderly? Abstract of the paper: Prevalence of dementing illnesses is expected to grow due to aging of the population throughout the world. Vascular dementia and Alzheimer's disease share several risk factors and are nowadays considered two ends of a continuum rather than two distinct entities. Traditional cardiovascular risk markers such as diabetes, dyslipidemia, hypertension, metabolic syndrome and adiposity in mid-life are harbingers of cognitive decline, Alzheimer's disease and vascular dementia later in life. In aged populations, only diabetes has been more constantly associated with the development of cognitive dysfunction, while other risk markers have shown more mixed results. Normal aging, co-morbidities and other changes connected to cognitive decline make the interpretation of the risk markers in the elderly challenging and probably explain these contradictory findings. Control of cardiovascular risk factors has been linked to beneficial effects in terms of cognition in cross-sectional and prospective follow up studies, but the results of interventional trials have been disappointing. More research in this area is needed, specifically, placebo-controlled randomized trials in both mid-life and late-life with cognitive dysfunction as a primary endpoint.

False

CitationGPTRetr11203

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular risk factors for Alzheimer's disease. Abstract of the paper: There is now sizable literature on the association between traditional cardiovascular risk factors and Alzheimer's disease (AD). Based on epidemiologic studies, both cross-sectional and longitudinal, there are statistically significant correlations between the prevalence of AD and diabetes, hypercholesterolemia, hypertension, hyperhomocysteinemia, dietary saturated fats, cholesterol, antioxidants, alcohol consumption, smoking, physical activity, the presence of atrial fibrillation, atherosclerotic disease, and the plasma concentration of some hemostatic factors. Most of the cardiovascular risk factors found to be associated with AD are age-dependent, and the prevalence of AD increases with age. Therefore, the association could simply be attributed to aging. On the other hand, the common pathogenetic mechanisms for the generation of both atherosclerotic disease and AD, such as inflammation and the generation of free radicals, suggest a causal link. If this is the case, the identification of modifiable risk factors for dementia becomes a research priority and early intervention aimed at reducing those cardiovascular risk factors a therapeutic imperative.

False

CitationGPTRetr11204

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular dementia - a different perspective. Abstract of the paper: The number of dementia patients has been growing in recent years and dementia represents a significant threat to aging people all over the world. Recent research has shown that the number of people affected by Alzheimer's disease (AD) and dementia is growing at an epidemic pace. The rapidly increasing financial and personal costs will affect the world's economies, health care systems, and many families. Researchers are now exploring a possible connection among AD, vascular dementia (VD), diabetes mellitus (type 2, T2DM) and cardiovascular diseases (CD). This correlation may be due to a strong association of cardiovascular risk factors with AD and VD, suggesting that these diseases share some biologic pathways. Since heart failure is associated with an increased risk of AD and VD, keeping the heart healthy may prove to keep the brain healthy as well. The risk for dementia is especially high when diabetes mellitus is comorbid with severe systolic hypertension or heart disease. In addition, the degree of coronary artery disease (CAD) is independently associated with cardinal neuropathological lesions of AD. Thus, the contribution of T2DM and CD to AD and VD implies that cardiovascular therapies may prove useful in preventing AD and dementia.

False

CitationGPTRetr11205

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular disease and Alzheimer's disease: common links. Abstract of the paper: Growing evidence supports a strong and likely causal association between cardiovascular disease (CVD), and its risk factors, with incidence of cognitive decline and Alzheimer's disease. Individuals with subclinical CVD are at higher risk for dementia and Alzheimer's. Several cardiovascular risk factors are also risk factors for dementia, including hypertension, high LDL cholesterol, low HDL cholesterol and especially diabetes. Moderate alcohol appears to be protective for both CVD and dementia. In contrast, inflammatory markers predict cardiovascular risk, but not dementia, despite biological plausibility for such a link. The substantial overlap in risk factors points to new avenues for research and prevention.

False

CitationGPTRetr11206

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: The metabolic syndrome and Alzheimer disease. Abstract of the paper: BACKGROUND The metabolic syndrome is a risk factor for cardiovascular diseases, which have been linked to Alzheimer disease. However, a link between Alzheimer disease and the metabolic syndrome has not yet been established. OBJECTIVE To investigate the relationship between the metabolic syndrome and Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTS Case-control study of 50 consecutive patients diagnosed with probable Alzheimer disease from the Memory Disorders Clinics, Launceston, Australia, and Bristol, England, and 75 cognitively normal controls. MAIN OUTCOME MEASURES The odds ratio of the metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III. RESULTS Compared with controls, patients with Alzheimer disease had a significantly larger mean waist circumference, higher mean plasma concentrations of triglycerides and glucose, and a lower mean plasma concentration of high-density lipoprotein cholesterol, but they had lower mean systolic blood pressure. The metabolic syndrome was associated with Alzheimer disease (odds ratio, 3.2; 95% confidence interval, 1.2-8.4; P = .02), and this association was strengthened when the hypertension component was excluded (odds ratio, 7.0; 95% confidence interval, 2.7-18.3; P < .001). All of the analyses were adjusted for age, sex, and location. CONCLUSIONS This study suggests that Alzheimer disease is associated with the metabolic syndrome. This could have implications for the prevention and treatment of Alzheimer disease.

False

CitationGPTRetr11207

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular risk factors and future risk of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD.

False

CitationGPTRetr11208

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular Disease Risk Factors and Cognition in the Elderly. Abstract of the paper: While it is relatively widely known that cardiovascular disease (CVD) can result in cognitive decline, it is becoming increasingly clearer that actual risk factors for CVD, such as high blood pressure, diabetes, and obesity are also associated with alterations to brain structure and cognition. The prevalence of CVD risk factors increase exponentially with age and are often overlooked as a source of cognitive changes that are otherwise thought to be part of the 'normal' aging process. Associated cognitive changes are observed even at levels of risk that would be considered subclinical by current diagnostic convention, and are often significant enough to interfere with daily functional abilities. More importantly, if not controlled, CVD risk can lead to further decline, including cerebrovacsular disease and dementia. Thus, it is critically important to consider these factors in the elderly and we recommend more routine cognitive screenings, particularly when CVD risk factors are involved.

False

CitationGPTRetr11209

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: The metabolic syndrome, diabetes, and Alzheimer's disease. Abstract of the paper: BACKGROUND The metabolic syndrome (MS) is a cluster of metabolic abnormalities that has been controversially associated with Alzheimer's disease (AD), so the purpose of this report was to investigate the association between these two chronic diseases a sample of older persons. METHODS Case-control study of 90 consecutive outpatients with AD and 180 non-demented controls from a dementia clinic at a tertiary care hospital in Mexico City. Probable or possible AD was diagnosed according to the guidelines of the Consortium to Establish a Registry for Alzheimer's Disease, whereas control participants where those classified as normal by the same instrument. MS was defined according to the World Health Organization criteria. Patients were matched 1:2 by age, sex, and years of education. Conditional regression analysis was used to test the association between MS and AD. RESULTS Compared to controls, MS was more frequent among AD patients (72.2% vs. 23.3%; P < 0.01). While all components of MS were more frequent among cases than control patients, only diabetes was statistically significant, whereas hypertriglyceridemia and low HDL cholesterol were marginally associated. Conditional regression analysis showed that among AD participants, the probability of having MS was about sevenfold higher than for their non-demented counterparts (OR 6.72, 95% CI 3.72-12.13; P < 0.01). CONCLUSIONS The MS is a clinical entity that encompasses a diverse range of chronic diseases, which could be a better risk indicator than any individual MS component for adverse health outcomes, like AD. Our findings underscore the harmful role of MS in the health status of the elderly.

True

CitationGPTRetr11210

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Midlife vascular risk factors and Alzheimer's disease: evidence from epidemiological studies. Abstract of the paper: The shared risk factor profile between cardiovascular diseases and Alzheimer's disease (AD), observations on vascular pathology in AD, and altered cerebral blood flow in AD brains have led to the suggestion that AD might be a vascular disorder with neurodegenerative consequences. Targeting vascular and metabolic risk factors could be an effective way to prevent AD. Higher body mass index, elevated blood pressure, serum cholesterol concentrations, and impaired glucose regulation have been associated with increased risk of AD. Interestingly, the associations between these factors measured at mid-life are stronger, or even opposite, than with the risk factors measured at late-life. This may reflect true differences in the association (i.e., mid-life risk factors being a better measure of vascular load during adulthood), reverse causality, or bias. The vascular risk factors can directly increase the susceptibility to AD, or the effect can be mediated via cardio- and cerebrovascular diseases.

False

CitationGPTRetr11211

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiac disorders as risk factors for Alzheimer's disease. Abstract of the paper: Vascular risk factors can play an important role in determining the onset of non-genetic Alzheimer's disease (AD). Most cases of AD are sporadic and late-onset, and a complex interaction between genetic predisposition and vascular risk factors has been proposed. Vascular risk factors for AD include stroke, hypertension, diabetes, homocysteine, smoking, hypercholesterolemia, heart failure and atrial fibrillation; it is possible that these can trigger cerebrovascular dysfunction and AD pathology. Explanations for these associations include the coincidence of common disorders in the elderly where vascular and cerebrovascular disease can precipitate AD, implying that the onset of dementia disease is determined by a synergistic combination of risk factors. In this paper we review the role of cardiovascular risk factors in the pathogenesis of AD and discuss the associated brain mechanisms that can underlie the onset of AD. Cardiovascular diseases are a promising avenue of AD research because they are potentially modifiable in early adult life and provide a new perspective for the prevention of dementia.

False

CitationGPTRetr11212

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: The role of cardiovascular risk factors in Alzheimer's disease. Abstract of the paper: The distinction between Alzheimer's disease and vascular dementia, the two most common types of dementia, has been undermined by recent advances in epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular risk factors, traditionally regarded as distinguishing criteria between the two entities, have been shown to be associated with both AD and vascular dementia. In this article, we propose mechanisms of action of cardiovascular risk factors in AD, suggest possible explanations for the overlap with vascular dementia and discuss the implications this might have on future differential diagnosis, research, and treatment strategies.

False

CitationGPTRetr11213

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: The dementia of cardiac disease. Abstract of the paper: Cardiovascular disease and dementia are common in the elderly and are major causes of disability in the general population. The public health burden of dementia is projected to increase as life expectancy increases in the United States and elsewhere. Epidemiological studies suggest that these once believed unrelated conditions, heart disease and dementia, may be linked by shared common risks and pathogenic elements. These observations have sparked the notion that prevention or modification of certain vascular risk factors and proper management of cardiovascular disease may prevent the development or progression of dementia including Alzheimer's disease. In this article, the authors discuss the association between cognitive impairment and atrial fibrillation, coronary artery disease, congestive heart failure, and cardiovascular procedures.

False

CitationGPTRetr11214

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cognitive impairment and cardiovascular diseases in the elderly. A heart-brain continuum hypothesis. Abstract of the paper: The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized.

False

CitationGPTRetr11215

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Peripheral cholesterol, metabolic disorders and Alzheimer's disease. Abstract of the paper: Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that, altogether, constitute a major cause of death in our societies.

False

CitationGPTRetr11216

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular disease risk factors and cognitive impairment. Abstract of the paper: The role of cardiovascular disease risk factors in the occurrence and progression of cognitive impairment has been the subject of a significant number of publications but has not achieved widespread recognition among many physicians and educated laymen. It is apparent that the active treatment of certain of these cardiovascular disease risk factors is accompanied by a reduced risk for cognitive impairment. Patients with hypertension who are treated experience fewer cardiovascular disease events as well as less cognitive impairment than similar untreated patients. Patients who exercise may present with less cognitive impairment, and obesity may increase the risk for cognitive impairment. Lipid abnormalities and genetic markers are associated with an increased risk for cardiovascular disease and cognitive impairment. Autopsy studies have demonstrated a correlation between elevated levels of cholesterol and amyloid deposition in the brain. Research has demonstrated a relation between atherosclerotic obstruction lesions in the circle of Willis and dementia. Diabetes mellitus is associated with an increased risk for cardiovascular disease and cognitive impairment. A number of nonpharmacologic factors have a role in reducing the risk for cognitive impairment. Antioxidants, fatty acids, and micronutrients may have a role, and diets rich in fruits and vegetables and other dietary approaches may improve the outlook for patients considered at risk for cognitive impairment.

False

CitationGPTRetr11217

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Cardiovascular disease and risk of Alzheimer's disease. Abstract of the paper: Several recent studies demonstrate associations between cardiovascular disease and its risk factors and the incidence of Alzheimer's disease. This review will examine the evidence for these associations and possible pathogenetic pathways. Clinical relevance and implications of these associations will also be discussed.

False

CitationGPTRetr11218

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Alzheimer's dementia: pathogenesis and impact of cardiovascular risk factors on cognitive decline. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia manifesting as alterations in cognitive abilities, behavior, and deterioration in memory which is progressive, leading to gradual worsening of symptoms. Major pathological features of AD are accumulations of neuronal amyloid plaques and neurofibrillary tangles, with early lesions appearing primarily in the hippocampus, the area of the brain involved in memory and learning. Cardiovascular-related risk factors are believed to play a crucial role in disease development and the acceleration of cognitive deterioration by worsening cerebral perfusion, promoting disturbances in amyloid clearance. Current evidence supports hypertension, hypotension, heart failure, stroke and coronary artery diseases as potential factors playing a role in cognitive decline in patients with Alzheimer's dementia. Although dementia due to cardiovascular deficits is more strongly linked to the development of vascular dementia, a stepwise decline in cognition, recent researches have also discovered its deleterious influence on AD development.

False

CitationGPTRetr11219

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cardiovascular diseases and metabolic conditions such as diabetes and dyslipidemia were highly prevalent in our study patients and this is in accordance with a growing body of literature which indicates that ad patients are likely to have an even worse cardiovascular and metabolic profile compared to elderly individuals who are not cognitively impaired Title of the paper: Vascular risk factors, cognitive decline, and dementia. Abstract of the paper: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer's disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer's disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.

False

CitationGPTRetr11220

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation. Abstract of the paper: Increased Ser phosphorylation of tau microtubule-associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B2 receptor activation leads to selective Ser phosphorylation of tau in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in tau Ser phosphorylation reflects modification of the G protein-coupled BK B2 receptors themselves. Both the BK B2 receptor modification and BK-mediated tau Ser phosphorylation are dependent on activation of protein kinase C and can be detected in fibroblasts from persons with Trisomy 21 two decades before the characteristic onset of AD. This dysregulated signaling cascade in AD may thus be expressed throughout life as an aberrant pathway in peripheral tissues more accessible than brain for molecular analysis. The sites of greatest BK B2 receptor expression in brain overlap with those areas displaying the earliest pathology in the course of AD, suggesting that BK receptor pathway dysfunction may be a molecular signature yielding information about the pathogenesis of AD.

False

CitationGPTRetr11221

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Mitogen-activated protein kinases and the evolution of Alzheimer's: a revolutionary neurogenetic axis for therapeutic intervention? Abstract of the paper: Alzheimer's disease (AD) is a neurogenetic condition that affects the processes via which the brain functions. Major observable hallmarks of AD are accumulated clusters of proteins in the brain. These clusters, termed neurofibrillary tangles (NFT), resemble pairs of threads wound around each other in a helix fashion accumulating within neurons. These tangles consist of a protein called Tau, which binds to tubulin, thus forming microtubules. Unlike NFTs, deposits of amyloid precursor protein (beta-APP) gather in the spaces between nerve cells. The nearby neurons often look swollen and deformed, and the clusters of protein are usually accompanied by reactive inflammatory cells, microglia, which are part of the brain's immune system responsible for degrading and removing damaged neurons or plaques. Since phosphorylation/dephosphorylation mechanisms are crucial in the regulation of Tau and beta-APP, a superfamily of mitogen-activated protein kinases (MAPKs) has recently emerged as key regulators of the formation of plagues, eventually leading to dementia and AD. The complex molecular interactions between MAPKs and proteins (plagues) associated with the evolution of AD form a cornerstone in the knowledge of a still burgeoning field of neurodegenerative diseases and ageing. This review overviews current understanding of the molecular pathways related to MAPKs and their role in the development of AD and, possibly, dementia. MAPKs, therefore, may constitute a neurogenetic, therapeutic target for the diagnosis and evolution of a preventative medical strategy for early detection, and likely treatment, of Alzheimer's.

False

CitationGPTRetr11222

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Distribution, levels and phosphorylation of Raf-1 in Alzheimer's disease. Abstract of the paper: Extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase pathway, has been increasingly implicated in the pathogenesis of Alzheimer's disease due to its critical role in brain function. While we previously demonstrated that ERK is activated in Alzheimer's disease, the upstream cascade leading to its activation had not been fully examined. In this study, we focused on Raf-1, one of the physiological activators of the ERK pathway. Raf-1 is activated by phosphorylation at Ser338 and Tyr340/341 and inhibited by phosphorylation at Ser259. Interestingly, phosphorylation at all three sites on Raf-1 was increased as evidenced by both immunocytochemistry and immunoblot analysis in Alzheimer's disease brains compared to age-matched controls. Both phospho-Raf-1 (Ser259) and phospho-Raf-1 (Ser338) were localized to intracytoplasmic granular structures, whereas phospho-Raf-1 (Tyr340/341) was localized to neurofibrillary tangles and granules in pyramidal neurons in Alzheimer's disease hippocampus. There is extensive overlap between phospho-Raf-1 (Ser338) and phospho-Mek1/2, the downstream effector of Raf-1, suggestive of a mechanistic link. Additionally, increased levels of Raf-1 are associated with Ras and MEK1 in Alzheimer's disease as evidenced by its coimmunoprecipitation with Ras and Mek1, respectively. Based on these findings, we speculate that Raf-1 is activated to effectively mediate Ras-dependent signals in Alzheimer's disease.

False

CitationGPTRetr11223

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease. Abstract of the paper: Serine-arginine protein kinases 2 (SRPK2) is a cell cycle-regulated kinase that phosphorylates serine/arginine domain-containing proteins and mediates pre-mRNA splicing with unclear function in neurons. Here, we show that SRPK2 phosphorylates tau on S214, suppresses tau-dependent microtubule polymerization, and inhibits axonal elongation in neurons. Depletion of SRPK2 in dentate gyrus inhibits tau phosphorylation in APP/PS1 mouse and alleviates the impaired cognitive behaviors. The defective LTP in APP/PS1 mice is also improved after SRPK2 depletion. Moreover, active SRPK2 is increased in the cortex of APP/PS1 mice and the pathological structures of human Alzheimer's disease (AD) brain. Therefore, our study suggests SRPK2 may contribute to the formation of hyperphosphorylated tau and the pathogenesis of AD.

False

CitationGPTRetr11224

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Localization of the mitogen activated protein kinase ERK2 in Alzheimer's disease neurofibrillary tangles and senile plaque neurites. Abstract of the paper: The phosphorylation of normal tau by mitogen activated protein (MAP) or extracellular signal related kinases (ERKs) induces tau to acquire biochemical properties of Alzheimer's disease (AD) paired helical filament (PHF) proteins in vitro. We show here that a monoclonal antibody to MAP kinases recognizes ERK2 in normal and AD cortex, but ERK2 levels are slightly reduced in the AD brain. Since ERK2 was detected in neurofibrillary tangles and senile plaque neurites in the AD hippocampus, ERK2 is positioned to phosphorylate normal tau and could play a role in the generation of PHFs in AD.

False

CitationGPTRetr11225

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Akt/GSK3beta serine/threonine kinases: evidence for a signalling pathway mediated by familial Alzheimer's disease mutations. Abstract of the paper: Although Alzheimer's disease pathologically affects the brain, familial Alzheimer's disease associated mutations of beta-amyloid precursor protein and presenilin are ubiquitously expressed and therefore aberrant intracellular signals, separate from but similar to, the brain may be expected. Here, we report selective down regulation of the serine/threonine kinase, Akt/PKB, concurrent with elevated endogenous GSK3beta kinase activity in familial Alzheimer's disease beta-amyloid precursor protein expressing human embryonic kidney (HEK) and familial Alzheimer's disease presenilin lymphoblast cells. Further, familial Alzheimer's disease presenilin in the human lymphoblast was associated with beta-catenin destabilization. Moreover, limited immunohistochemistry analysis reveals Akt/PKB in a subset of neurofibrillary tangles where GSK3beta and tau have been reported to co-localize, suggesting a possible Akt/GSK3beta and tau interaction in vivo. Our data suggest that familial Alzheimer's disease mutants of beta-amyloid precursor protein and presenilin signal, at least in part, through the Akt/GSKbeta pathway and that Akt/GSK3beta-mediated signalling may contribute to the underlying Alzheimer's disease pathogenesis induced by familial Alzheimer's disease mutants.

False

CitationGPTRetr11226

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Receptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer's disease and type 2 diabetes. Abstract of the paper: Alzheimer's disease (AD) and type 2 diabetes (T2D) share the common hallmark of insulin resistance. It is conjectured that receptor tyrosine kinases (RTKs) play definitive roles in the process. To decipher the signaling overlap behind this phenotypic resemblance, the activity status of RTKs is probed in post-mortem AD and T2D tissues and cell models. Activities of only about one-third changed in a similar fashion, whereas about half of them showed opposite outcomes when exposed to contrasting signals akin to AD and T2D. Interestingly, irrespective of disease type, RTKs with enhanced and compromised activities clustered distinctly, indicating separate levels of regulations. Similar regulatory mechanisms within an activity cluster could be inferred, which have potential to impact future therapeutic developments.

False

CitationGPTRetr11227

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Elevated expression of p21ras is an early event in Alzheimer's disease and precedes neurofibrillary degeneration. Abstract of the paper: Alzheimer's disease is a chronic degenerative disorder characterized by the intracellular accumulation of "paired helical filaments" consisting of highly phosphorylated tau and by extracellular deposits of aggregated Abeta-peptide. Furthermore, neurodegeneration in Alzheimer's disease is associated with the appearance of neuritic growth profiles that are aberrant with respect to their localization, morphological appearance, and composition of cytoskeletal elements. During early stages of Alzheimer's disease, a variety of growth factors and mitogenic compounds are elevated. Most of these factors mediate their cellular effects through activation of the p21ras-dependent mitogen-activated protein kinase cascade, a pathway that is also involved in the regulation of expression and post-translational modification of the amyloid precursor protein and tau protein. We previously reported on the elevated expression of p21ras associated with paired helical filament formation and Abeta-deposits. However, the question arises as to whether induction of p21ras and the downstream mitogen-activated protein kinase cascade is an early event with rather primary importance in the pathogenetic chain or simply occurs as a cellular response to neurodegeneration. The present study shows that expression of p21ras is clearly elevated in very early stages of the disease, preceding both neurofibrillary pathology and formation of Abeta.

False

CitationGPTRetr11228

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer's disease fibroblasts. Abstract of the paper: Abnormal protein kinase C levels and protein kinase C-dependent phosphorylation are biochemical alterations in brain tissue obtained from patients with Alzheimer's disease. Because many biochemical and biophysical abnormalities are found in peripheral tissues of patients with Alzheimer's disease, we studied protein kinase C levels and the in vitro phosphorylation of proteins under protein kinase C-activating conditions in fibroblasts derived from patients with Alzheimer's disease. The concentration of protein kinase C-like immunoreactivity was reduced in Alzheimer's disease samples, although the protein kinase C activity determined by the phosphorylation of exogenous histone was not. The degree of in vitro phosphorylation of an Mr 79,000 protein in the presence of protein kinase C activators was less in Alzheimer's disease than in control fibroblast cytosol, and a reduction was more prominent in cases of familial Alzheimer's disease than in sporadic Alzheimer's disease. Therefore, the aberrant phosphorylation mediated by protein kinase C is found not only in the brain but also in fibroblasts.

False

CitationGPTRetr11229

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Abnormal Tau phosphorylation of the Alzheimer-type also occurs during mitosis. Abstract of the paper: In Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into filaments and it may be related to the reactivation of mitotic mechanisms. In order to investigate the link between Tau phosphorylation and mitosis, Xenopus laevis oocytes in which most of the M-phase regulators have been discovered were used as a cell model. The human Tau isoform htau412 (2+3-10+) was microinjected into prophase I oocytes that were then stimulated by progesterone that activate cyclin-dependent kinase pathways. Hyperphosphorylation of the Tau isoform, which is characterized by a decrease of its electrophoretic mobility and its labelling by a number of phosphorylation-dependent antibodies, was observed at the time of germinal vesicle breakdown. Surprisingly, Tau immunoreactivity, considered as typical of Alzheimer's pathology (AT100 and phospho-Ser422), was observed in meiosis II. Because meiosis II is considered as a mitosis-like phase, we investigated if our observation was also relevant to a neurone-like model. Abnormal Tau phosphorylation was detected in mitotic human neuroblastoma SY5Y cells overexpressing Tau. Regarding AT100-immunoreactivity and phospho-Ser422, we suggest that phosphatase 2A inhibition and a phosphorylation combination of mitotic kinases may lead to this Alzheimer-type phosphorylation. Our results not only demonstrate the involvement of mitotic kinases in Alzheimer-type Tau phosphorylation but also indicate that Xenopus oocyte could be a useful model to identify the kinases involved in this process.

False

CitationGPTRetr11230

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: A new molecular link between the fibrillar and granulovacuolar lesions of Alzheimer's disease. Abstract of the paper: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder involving select neurons of the hippocampus, neocortex, and other regions of the brain. Markers of end stage disease include fibrillar lesions, which accumulate hyperphosphorylated tau protein polymerized into filaments, and granulovacuolar lesions, which appear primarily within the hippocampus. The mechanism by which only select populations of neurons develop these lesions as well as the relationship between them is unknown. To address these questions, we have turned to AD tissue to search for enzymes specifically involved in tau hyperphosphorylation. Recently, we showed that the principal phosphotransferases associated with AD brain-derived tau filaments are members of the casein kinase-1 (CK1) family of protein kinases. Here we report the distribution of three CK1 isoforms (Ckialpha, Ckidelta, and Ckiepsilon) in AD and control brains using immunohistochemistry and Western analysis. In addition to colocalizing with elements of the fibrillar pathology, CK1 is found within the matrix of granulovacuolar degeneration bodies. Furthermore, levels of all CK1 isoforms are elevated in the CA1 region of AD hippocampus relative to controls, with one isoform, Ckidelta, being elevated >30-fold. We propose that overexpression of this protein kinase family plays a key role in the hyperphosphorylation of tau and in the formation of AD-related pathology.

False

CitationGPTRetr11231

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease. Abstract of the paper: Double-stranded RNA dependent kinase (PKR) is a pro-apoptotic kinase that controls protein translation. Previous studies revealed that activated PKR is increased in brains with Alzheimer's disease (AD). Glycogen Synthase Kinase Aβ (GSK-3β) is responsible for tau phosphorylation and controls several cellular functions also including apoptosis. The goal of this work was to determine if PKR could concurrently trigger GSK-3β activation, tau phosphorylation and apoptosis. In AD brains, both activated kinases co-localize with phosphorylated tau in neurons. In SH-SY5Y cell cultures, tunicamycin and Aβ(1-42) activate PKR, GSK-3β and induce tau phosphorylation and all these processes are attenuated by PKR inhibitors or PKR siRNA. Our results demonstrate that neuronal PKR co-localizes with GSK-3β and tau in AD brains and is able to modulate GSK-3β activation, tau phosphorylation and apoptosis in neuroblastoma cells exposed to tunicamycin or Aβ. PKR could represent a crucial signaling point relaying stress signals to neuronal pathways leading to cellular degeneration in AD.

False

CitationGPTRetr11232

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease. Abstract of the paper: The abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) has been proposed to involve the extracellular-signal-regulated protein kinase (ERK) of the mitogen-activated protein (MAP) kinase family. ERK is phosphorylated and thereby activated by MAP kinase kinase (MEK). In the present study, we determined the intracellular and regional distribution of the active forms of both MEK1/2 and ERK1/2, i.e. p-MEK1/2 and p-ERK1/2 in the entorhinal, hippocampal, and temporal cortices of 49 brains staged for neurofibrillary changes according to Braak and Braak's protocol. We found that p-MEK1/2 and p-ERK1/2 were present in the initial stages of neurofibrillary degeneration in the projecting neurons in the transentorhinal region, and extended into other brain regions co-incident with the progressive sequence of neurofibrillary changes up to and including Braak stage VI. It appeared that the accumulation of p-MEK1/2 and p-ERK1/2 was initiated in the cytoplasm of pretangle neurons in varying size granules, which grew into large aggregates co-existing with the progressive development of neurofibrillary tangles. Accumulation of p-MEK1/2 and p-ERK1/2 was found in cases with stages I-III neurofibrillary degeneration, which were devoid of amyloid deposition. These data provide direct in situ evidence consistent with the possible involvement of MAP kinase pathway in the hyperphosphorylation of tau and the presence of this lesion before deposition of beta-amyloid in AD.

False

CitationGPTRetr11233

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Role of protein kinase B in Alzheimer's neurofibrillary pathology. Abstract of the paper: Protein kinase B (PKB) is an important intermediate in the phosphatidylinositol-3 kinase signaling cascade that acts to phosphorylate glycogen synthase kinase-3 (GSK-3) at its serine 9 residue, thereby inactivating it. Activated GSK-3 has been previously shown to be preferentially associated with neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brain. In the present study, we performed immunohistochemistry with an antibody to the active form of PKB in brains with different stages of neurofibrillary degeneration. We found that the amount of activated PKB (p-Thr308) increased in correlation to the progressive sequence of AT8 immunoreactivity and neurofibrillary changes assessed according to Braak's criteria. By confocal microscopy, activated PKB (p-Thr308) was found to appear in particular in neurons that are known to later develop NFTs in AD. Western blotting showed that activated PKB was increased by more than 50% in the 16,000- g supernatants of AD brains as compared with normal aged and Huntington's disease controls. This increase in PKB levels corresponded with a several-fold increase in the levels of total tau and abnormally hyperphosphorylated tau at the Tau-1 site. These studies suggest the involvement of PKB/GSK-3 signaling in Alzheimer neurofibrillary degeneration.

False

CitationGPTRetr11234

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Cyclic AMP-dependent protein kinase regulates the alternative splicing of tau exon 10: a mechanism involved in tau pathology of Alzheimer disease. Abstract of the paper: Hyperphosphorylation and deposition of tau into neurofibrillary tangles is a hallmark of Alzheimer disease (AD). Alternative splicing of tau exon 10 generates tau isoforms containing three or four microtubule binding repeats (3R-tau and 4R-tau), which are equally expressed in adult human brain. Dysregulation of exon 10 causes neurofibrillary degeneration. Here, we report that cyclic AMP-dependent protein kinase, PKA, phosphorylates splicing factor SRSF1, modulates its binding to tau pre-mRNA, and promotes tau exon 10 inclusion in cultured cells and in vivo in rat brain. PKA-Cα, but not PKA-Cβ, interacts with SRSF1 and elevates SRSF1-mediated tau exon 10 inclusion. In AD brain, the decreased level of PKA-Cα correlates with the increased level of 3R-tau. These findings suggest that a down-regulation of PKA dysregulates the alternative splicing of tau exon 10 and contributes to neurofibrillary degeneration in AD by causing an imbalance in 3R-tau and 4R-tau expression.

False

CitationGPTRetr11235

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. Abstract of the paper: Tau in Alzheimer disease brain is highly phosphorylated and aggregated into paired helical filaments comprising characteristic neurofibrillary tangles. Here we have analyzed insoluble Tau (PHF-tau) extracted from Alzheimer brain by mass spectrometry and identified 11 novel phosphorylation sites, 10 of which were assigned unambiguously to specific amino acid residues. This brings the number of directly identified sites in PHF-tau to 39, with an additional six sites indicated by reactivity with phosphospecific antibodies to Tau. We also identified five new phosphorylation sites in soluble Tau from control adult human brain, bringing the total number of reported sites to nine. To assess which kinases might be responsible for Tau phosphorylation, we used mass spectrometry to determine which sites were phosphorylated in vitro by several kinases. Casein kinase 1delta and glycogen synthase kinase-3beta were each found to phosphorylate numerous sites, and each kinase phosphorylated at least 15 sites that are also phosphorylated in PHF-tau from Alzheimer brain. A combination of casein kinase 1delta and glycogen synthase kinase-3beta activities could account for over three-quarters of the serine/threonine phosphorylation sites identified in PHF-tau, indicating that casein kinase 1delta may have a role, together with glycogen synthase kinase-3beta, in the pathogenesis of Alzheimer disease.

False

CitationGPTRetr11236

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Double stranded RNA activated EIF2 alpha kinase (EIF2AK2; PKR) is associated with Alzheimer's disease. Abstract of the paper: Sporadic Alzheimer's disease (AD) appears to be the consequence of the interaction between combinations of genes and environmental factors (for example virus infections). To test this hypothesis, we are examining human genes relevant to herpes simplex virus type 1 (HSV-1) infection via genetic association studies in AD case-control samples. Recently, we found that a variant in TAP2, a major target used by HSV-1 to evade immune surveillance, is associated with AD. The present work analyses another gene involved in the host cell response to HSV-1, EIF2AK2 (eukaryotic translation initiation factor 2-alpha kinase 2; coding for PKR); PKR mediates the virus-induced shut-off of translation, and levels of activated PKR are high in the brains of AD patients. An EIF2AK2 SNP (rs2254958) located in the 5'-UTR region within an exonic splicing enhancer was found to be associated with AD. More specifically: the C allele was more commonly found in the patients and, compared to non-CC genotypes, the CC homozygotes showed earlier (around 3.3 years) onset of AD, especially in the absence of the APOE4 allele. These results further support the hypothesis that variants of human genes participating in HSV-1 infection modulate the susceptibility and/or clinical manifestations of AD.

False

CitationGPTRetr11237

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease. Abstract of the paper: Most individuals with Down syndrome show early onset of Alzheimer disease (AD), resulting from the extra copy of chromosome 21. Located on this chromosome is a gene that encodes the dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). One of the pathological hallmarks in AD is the presence of neurofibrillary tangles (NFTs), which are insoluble deposits that consist of abnormally hyperphosphorylated Tau. Previously it was reported that Tau at the Thr-212 residue was phosphorylated by Dyrk1A in vitro. To determine the physiological significance of this phosphorylation, an analysis was made of the amount of phospho-Thr-212-Tau (pT212) in the brains of transgenic mice that overexpress the human DYRK1A protein (DYRK1A TG mice) that we recently generated. A significant increase in the amount of pT212 was found in the brains of DYRK1A transgenic mice when compared with age-matched littermate controls. We further examined whether Dyrk1A phosphorylates other Tau residues that are implicated in NFTs. We found that Dyrk1A also phosphorylates Tau at Ser-202 and Ser-404 in vitro. Phosphorylation by Dyrk1A strongly inhibited the ability of Tau to promote microtubule assembly. Following this, using mammalian cells and DYRK1A TG mouse brains, it was demonstrated that the amounts of phospho-Ser-202-Tau and phospho-Ser-404-Tau are enhanced when DYRK1A amounts are high. These results provide the first in vivo evidence for a physiological role of DYRK1A in the hyperphosphorylation of Tau and suggest that the extra copy of the DYRK1A gene contributes to the early onset of AD.

False

CitationGPTRetr11238

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: Genetic association of neurotrophic tyrosine kinase receptor type 2 (NTRK2) With Alzheimer's disease. Abstract of the paper: Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase (TRK) signaling pathway activates a wide range of downstream intracellular cascades, regulating neuronal development and plasticity, long-term potentiation, and apoptosis. The NTRK family encodes the receptors TRKA, TRKB, and TRKC, to which the neurotrophins, nerve growth factor (NGF), BDNF and neurotrophin-3 (NT-3) bind, respectively, with high affinity. Signaling through these receptors appears to be compromised in Alzheimer's disease (AD). This study is the most comprehensive investigation of genetic variants of NTRK2, and the first to show significant association between NTRK2 with AD. Fourteen single nucleotide polymorphisms (SNPs), located in 8 of 18 linkage disequilibrium (LD) blocks, were genotyped in 203 families with at least two AD affected siblings with mean age of onset (MAO) of 70.9 +/- 7.4 years and one unaffected sibling from the NIMH-ADGJ dataset. Family based association testing found no single SNP association, however, significant associations were found for two and three locus haplotypes (P = 0.012, P = 0.009, respectively) containing SNPs rsl624327, rsl443445, and rs378645. These SNPs are located in areas of the gene containing sequences that could be involved in alternative splicing and/or regulation of NTRK2. Our results suggest that NTRK2 may be a genetic susceptibility gene contributing to AD pathology.

False

CitationGPTRetr11239

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bcr and csk variants have also been associated with ad Title of the paper: A Study Investigating the Role of 2 Candidate SNPs in Bax and Bcl-2 Genes in Alzheimer's Disease. Abstract of the paper: OBJECTIVE The proto-oncogene Bax (Bcl-2-associated X protein) and related protein Bcl-2 (B-cell chronic lymphocytic leukemia/lymphoma-2) genes are triggers of apoptosis in Alzheimer's disease (AD). The balance of these proteins has an important role in the death or life of a neuronal cell, and the functional polymorphisms in genes expressing these proteins have been found to promote apoptosis. To investigate the role of Bax and Bcl-2 genes in AD, we examined the presence of the 2 polymorphisms in peripheral blood. To our knowledge, this is the first clinical association study of these 2 functional SNPs using the peripheral blood of patients with AD. METHODS Bax (rs4645878) and Bcl-2 (rs2279115) in Alzheimer's patients (N = 132) and healthy controls (N = 109), aged 65 to 85 years, were analyzed by qPCR (Quantitative Polymerase Chain Reaction) using TaqMan probe technology. Statistical analyses were done using SPSS, 11.5. The differences between groups were analyzed using an independent-samples t test. The relationships between genotypes and alleles were analyzed using chi-square or likelihood ratio test. The Hardy-Weinberg balance was checked for the patient and control groups. A p-value of less than 0.05 was taken as significant. RESULTS Sporadic AD patients and non-demented age matched control subjects were genotyped in this case-control study. No statistically significant relationship was found between the patients and controls for allele or genotype frequencies (p>0.05). CONCLUSION Our data suggest that these two polymorphisms do not contribute to AD in the population from the Mersin region of the Eastern Mediterranean. Further studies with larger sample sizes must be conducted to ascertain the association between the 2 polymorphisms.

False

CitationGPTRetr11240

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Powering membrane traffic in endocytosis and recycling. Abstract of the paper: Early in evolution, the diversification of membrane-bound compartments that characterize eukaryotic cells was accompanied by the elaboration of molecular machineries that mediate intercompartmental communication and deliver materials to specific destinations. Molecular motors that move on tracks of actin filaments or microtubules mediate the movement of organelles and transport between compartments. The subjects of this review are the motors that power the transport steps along the endocytic and recycling pathways, their modes of attachment to cargo and their regulation.

False

CitationGPTRetr11241

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Motors and membrane traffic. Abstract of the paper: The cytoskeleton is essential for the proper function of many components of secretory and endocytic pathways, and the importance both of microtubule motors (kinesins and dyneins) and of actin motors (myosins) in these pathways is becoming apparent. Recent experiments have improved our understanding of which members of these motor protein families are involved in membrane traffic. Multiple motors are probably involved in the control of the morphology and dynamics of many membranes, and intriguing hints about how these motors are coordinated are appearing.

False

CitationGPTRetr11242

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Axonal transport: Driving synaptic function. Abstract of the paper: The intracellular transport system in neurons is specialized to an extraordinary degree, enabling the delivery of critical cargo to sites in axons or dendrites that are far removed from the cell center. Vesicles formed in the cell body are actively transported by kinesin motors along axonal microtubules to presynaptic sites that can be located more than a meter away. Both growth factors and degradative vesicles carrying aged organelles or aggregated proteins take the opposite route, driven by dynein motors. Distance is not the only challenge; precise delivery of cargos to sites of need must also be accomplished. For example, localized delivery of presynaptic components to hundreds of thousands of "en passant" synapses distributed along the length of a single axon in some neuronal subtypes provides a layer of complexity that must be successfully navigated to maintain synaptic transmission. We review recent advances in the field of axonal transport, with a focus on conceptual developments, and highlight our growing quantitative understanding of neuronal trafficking and its role in maintaining the synaptic function that underlies higher cognitive processes such as learning and memory.

False

CitationGPTRetr11243

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: The axonal transport of mitochondria. Abstract of the paper: Organelle transport is vital for the development and maintenance of axons, in which the distances between sites of organelle biogenesis, function, and recycling or degradation can be vast. Movement of mitochondria in axons can serve as a general model for how all organelles move: mitochondria are easy to identify, they move along both microtubule and actin tracks, they pause and change direction, and their transport is modulated in response to physiological signals. However, they can be distinguished from other axonal organelles by the complexity of their movement and their unique functions in aerobic metabolism, calcium homeostasis and cell death. Mitochondria are thus of special interest in relating defects in axonal transport to neuropathies and degenerative diseases of the nervous system. Studies of mitochondrial transport in axons are beginning to illuminate fundamental aspects of the distribution mechanism. They use motors of one or more kinesin families, along with cytoplasmic dynein, to translocate along microtubules, and bidirectional movement may be coordinated through interaction between dynein and kinesin-1. Translocation along actin filaments is probably driven by myosin V, but the protein(s) that mediate docking with actin filaments remain unknown. Signaling through the PI 3-kinase pathway has been implicated in regulation of mitochondrial movement and docking in the axon, and additional mitochondrial linker and regulatory proteins, such as Milton and Miro, have recently been described.

False

CitationGPTRetr11244

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: The axonal transport of mitochondria. Abstract of the paper: Vigorous transport of cytoplasmic components along axons over substantial distances is crucial for the maintenance of neuron structure and function. The transport of mitochondria, which serves to distribute mitochondrial functions in a dynamic and non-uniform fashion, has attracted special interest in recent years following the discovery of functional connections among microtubules, motor proteins and mitochondria, and their influences on neurodegenerative diseases. Although the motor proteins that drive mitochondrial movement are now well characterized, the mechanisms by which anterograde and retrograde movement are coordinated with one another and with stationary axonal mitochondria are not yet understood. In this Commentary, we review why mitochondria move and how they move, focusing particularly on recent studies of transport regulation, which implicate control of motor activity by specific cell-signaling pathways, regulation of motor access to transport tracks and static microtubule-mitochondrion linkers. A detailed mechanism for modulating anterograde mitochondrial transport has been identified that involves Miro, a mitochondrial Ca(2+)-binding GTPase, which with associated proteins, can bind and control kinesin-1. Elements of the Miro complex also have important roles in mitochondrial fission-fusion dynamics, highlighting questions about the interdependence of biogenesis, transport, dynamics, maintenance and degradation.

False

CitationGPTRetr11245

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: The cytoplasmic dynein transport machinery and its many cargoes. Abstract of the paper: Cytoplasmic dynein 1 is an important microtubule-based motor in many eukaryotic cells. Dynein has critical roles both in interphase and during cell division. Here, we focus on interphase cargoes of dynein, which include membrane-bound organelles, RNAs, protein complexes and viruses. A central challenge in the field is to understand how a single motor can transport such a diverse array of cargoes and how this process is regulated. The molecular basis by which each cargo is linked to dynein and its cofactor dynactin has started to emerge. Of particular importance for this process is a set of coiled-coil proteins - activating adaptors - that both recruit dynein-dynactin to their cargoes and activate dynein motility.

False

CitationGPTRetr11246

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Role of actin in organelle trafficking in neurons. Abstract of the paper: Actin is a major cytoskeletal element involved in multiple cellular processes. Actin-rich regions present along the neuronal process aid in neuronal function, mediating multiple events involved in organelle trafficking. Actin is involved in organelle biogenesis, transport, and anchoring at specific locations. These functions can potentially be regulated by actin in a myosin-dependent or myosin-independent manner. The actin network could aid in membrane remodeling through membrane constriction, motor dependent transport, polymerization-based transport, cargo anchoring, and halting of cargo by acting as a physical barrier. Additionally, actin dynamics is perturbed in some neurodegenerative diseases where it could impact organelle biogenesis, transport, or anchoring thereby contributing to progression of disease phenotypes. The role of actin and myosin in organelle trafficking is the primary focus of this review.

False

CitationGPTRetr11247

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Moving mitochondria: establishing distribution of an essential organelle. Abstract of the paper: Mitochondria form a dynamic network responsible for energy production, calcium homeostasis and cell signaling. Appropriate distribution of the mitochondrial network contributes to organelle function and is essential for cell survival. Highly polarized cells, including neurons and budding yeast, are particularly sensitive to defects in mitochondrial movement and have emerged as model systems for studying mechanisms that regulate organelle distribution. Mitochondria in multicellular eukaryotes move along microtubule tracks. Actin, the primary cytoskeletal component used for transport in yeast, has more subtle functions in other organisms. Kinesin, dynein and myosin isoforms drive motor-based movement along cytoskeletal tracks. Milton and syntabulin have recently been identified as potential organelle-specific adaptor molecules for microtubule-based motors. Miro, a conserved GTPase, may function with Milton to regulate transport. In yeast, Mmr1p and Ypt11p, a Rab GTPase, are implicated in myosin V-based mitochondrial movement. These potential adaptors could regulate motor activity and therefore determine individual organelle movements. Anchoring of stationary mitochondria also contributes to organelle retention at specific sites in the cell. Together, movement and anchoring ultimately determine mitochondrial distribution throughout the cell.

False

CitationGPTRetr11248

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Microtubule transport in the axon. Abstract of the paper: There has been a great deal of interest in how the microtubule array of the axon is established and maintained. In an early model, it was proposed that microtubules are actively transported from the cell body of the neuron down the length of the axon. This model has been contested over the years in favor of very different models based on stationary microtubules. It appears that a corner has finally been turned in this long-standing controversy. It is now clear that cells contain molecular motor proteins capable of transporting microtubules and that microtubule transport is an essential component in the formation of microtubule arrays across many cells types. A wide variety of cell biological approaches have provided strong indirect evidence that microtubules are indeed transported within axons, and new live-cell imaging approaches are beginning to permit the direct visualization of this transport. The molecules and mechanisms that transport microtubules within axons are also under intense study.

False

CitationGPTRetr11249

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Microtubule-based transport - basic mechanisms, traffic rules and role in neurological pathogenesis. Abstract of the paper: Microtubule-based transport is essential for neuronal function because of the large distances that must be traveled by various building blocks and cellular materials. Recent studies in various model systems have unraveled several regulatory mechanisms and traffic rules that control the specificity, directionality and delivery of neuronal cargos. Local microtubule cues, opposing motor activity and cargo-adaptors that regulate motor activity control microtubule-based transport in neurons. Impairment of intracellular transport is detrimental to neurons and has emerged as a common factor in several neurological disorders. Genetic approaches have revealed strong links between intracellular transport processes and the pathogenesis of neurological diseases in both the central and peripheral nervous system. This Commentary highlights recent advances in these areas and discusses the transport defects that are associated with the development of neurological diseases.

False

CitationGPTRetr11250

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: The microtubule cytoskeleton at the synapse. Abstract of the paper: In neurons, microtubules (MTs) provide routes for transport throughout the cell and structural support for dendrites and axons. Both stable and dynamic MTs are necessary for normal neuronal functions. Research in the last two decades has demonstrated that MTs play additional roles in synaptic structure and function in both pre- and postsynaptic elements. Here, we review current knowledge of the functions that MTs perform in excitatory and inhibitory synapses, as well as in the neuromuscular junction and other specialized synapses, and discuss the implications that this knowledge may have in neurological disease.

False

CitationGPTRetr11251

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Regulation of Axonal Transport by Protein Kinases. Abstract of the paper: The intracellular transport of organelles, proteins, lipids, and RNA along the axon is essential for neuronal function and survival. This process, called axonal transport, is mediated by two classes of ATP-dependent motors, kinesins, and cytoplasmic dynein, which carry their cargoes along microtubule tracks. Protein kinases regulate axonal transport through direct phosphorylation of motors, adapter proteins, and cargoes, and indirectly through modification of the microtubule network. The misregulation of axonal transport by protein kinases has been implicated in the pathogenesis of several nervous system disorders. Here, we review the role of protein kinases acting directly on axonal transport and discuss how their deregulation affects neuronal function, paving the way for the exploitation of these enzymes as novel drug targets.

False

CitationGPTRetr11252

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: ER - lysosome contacts at a pre-axonal region regulate axonal lysosome availability. Abstract of the paper: Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule - lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule - lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.

False

CitationGPTRetr11253

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Moonlighting Motors: Kinesin, Dynein, and Cell Polarity. Abstract of the paper: In addition to their well-known role in transporting cargoes in the cytoplasm, microtubule motors organize their own tracks - the microtubules. While this function is mostly studied in the context of cell division, it is essential for microtubule organization and generation of cell polarity in interphase cells. Kinesin-1, the most abundant microtubule motor, plays a role in the initial formation of neurites. This review describes the mechanism of kinesin-1-driven microtubule sliding and discusses its biological significance in neurons. Recent studies describing the interplay between kinesin-1 and cytoplasmic dynein in the translocation of microtubules are discussed. In addition, we evaluate recent work exploring the developmental regulation of microtubule sliding during axonal outgrowth and regeneration. Collectively, the discussed works suggest that sliding of interphase microtubules by motors is a novel force-generating mechanism that reorganizes the cytoskeleton and drives shape change and polarization.

False

CitationGPTRetr11254

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Kinesin molecular motors: transport pathways, receptors, and human disease. Abstract of the paper: Kinesin molecular motor proteins are responsible for many of the major microtubule-dependent transport pathways in neuronal and non-neuronal cells. Elucidating the transport pathways mediated by kinesins, the identity of the cargoes moved, and the nature of the proteins that link kinesin motors to cargoes are areas of intense investigation. Kinesin-II recently was found to be required for transport in motile and nonmotile cilia and flagella where it is essential for proper left-right determination in mammalian development, sensory function in ciliated neurons, and opsin transport and viability in photoreceptors. Thus, these pathways and proteins may be prominent contributors to several human diseases including ciliary dyskinesias, situs inversus, and retinitis pigmentosa. Kinesin-I is needed to move many different types of cargoes in neuronal axons. Two candidates for receptor proteins that attach kinesin-I to vesicular cargoes were recently found. One candidate, sunday driver, is proposed to both link kinesin-I to an unknown vesicular cargo and to bind and organize the mitogen-activated protein kinase components of a c-Jun N-terminal kinase signaling module. A second candidate, amyloid precursor protein, is proposed to link kinesin-I to a different, also unknown, class of axonal vesicles. The finding of a possible functional interaction between kinesin-I and amyloid precursor protein may implicate kinesin-I based transport in the development of Alzheimer's disease.

False

CitationGPTRetr11255

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Kinesin is the motor for microtubule-mediated Golgi-to-ER membrane traffic. Abstract of the paper: The distribution and dynamics of both the ER and Golgi complex in animal cells are known to be dependent on microtubules; in many cell types the ER extends toward the plus ends of microtubules at the cell periphery and the Golgi clusters at the minus ends of microtubules near the centrosome. In this study we provide evidence that the microtubule motor, kinesin, is present on membranes cycling between the ER and Golgi and powers peripherally directed movements of membrane within this system. Immunolocalization of kinesin at both the light and electron microscopy levels in NRK cells using the H1 monoclonal antibody to kinesin heavy chain, revealed kinesin to be associated with all membranes of the ER/Golgi system. At steady-state at 37 degrees C, however, kinesin was most concentrated on peripherally distributed, pre-Golgi structures containing beta COP and vesicular stomatitis virus glycoprotein newly released from the ER. Upon temperature reduction or nocodazole treatment, kinesin's distribution shifted onto the Golgi, while with brefeldin A (BFA)-treatment, kinesin could be found in both Golgi-derived tubules and in the ER. This suggested that kinesin associates with membranes that constitutively cycle between the ER and Golgi. Kinesin's role on these membranes was examined by microinjecting kinesin antibody. Golgi-to-ER but not ER-to-Golgi membrane transport was found to be inhibited by the microinjected anti-kinesin, suggesting kinesin powers the microtubule plus end-directed recycling of membrane to the ER, and remains inactive on pre-Golgi intermediates that move toward the Golgi complex.

False

CitationGPTRetr11256

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Autophagy and microtubules - new story, old players. Abstract of the paper: Both at a basal level and after induction (especially in response to nutrient starvation), the function of autophagy is to allow cells to degrade and recycle damaged organelles, proteins and other biological constituents. Here, we focus on the role microtubules have in autophagosome formation, autophagosome transport across the cytoplasm and in the formation of autolysosomes. Recent insights into the exact relationship between autophagy and microtubules now point to the importance of microtubule dynamics, tubulin post-translational modifications and microtubule motors in the autophagy process. Such factors regulate signaling pathways that converge to stimulate autophagosome formation. They also orchestrate the movements of pre-autophagosomal structures and autophagosomes or more globally organize and localize immature and mature autophagosomes and lysosomes. Most of the factors that now appear to link microtubules to autophagosome formation or to autophagosome dynamics and fate were identified initially without the notion that sequestration, recruitment and/or interaction with microtubules contribute to their function. Spatial and temporal coordination of many stages in the life of autophagosomes thus underlines the integrative role of microtubules and progressively reveals hidden parts of the autophagy machinery.

False

CitationGPTRetr11257

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: PATHOLOGIES OF AXONAL TRANSPORT IN NEURODEGENERATIVE DISEASES. Abstract of the paper: Gene products such as organelles, proteins and RNAs are actively transported to synaptic terminals for the remodeling of pre-existing neuronal connections and formation of new ones. Proteins described as molecular motors mediate this transport and utilize specialized cytoskeletal proteins that function as molecular tracks for the motor based transport of cargos. Molecular motors such as kinesins and dynein's move along microtubule tracks formed by tubulins whereas myosin motors utilize tracks formed by actin. Deficits in active transport of gene products have been implicated in a number of neurological disorders. We describe such disorders collectively as "transportopathies". Here we review current knowledge of critical components of active transport and their relevance to neurodegenerative diseases.

False

CitationGPTRetr11258

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Neuronal endosomes to lysosomes: A journey to the soma. Abstract of the paper: How are lysosomal degradation pathways spatially organized in the complex landscape of a neuron? Cheng et al. (2018. J Cell Biol. https://doi.org/10.1083/jcb.201711083) and Yap et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201711039) characterize the distribution and function of endolysosomal organelles in neurons, providing insights into compartment-specific mechanisms regulating the neuronal proteome.

False

CitationGPTRetr11259

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: these motors can transport their cargoes for example mitochondria 46 47 lysosomes 48 peroxisomes 49 and endocytotic or exocytotic vesicles towards the cell periphery or back towards the microtubule organizing center mtoc respectively Title of the paper: Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons. Abstract of the paper: To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150(Glued) suggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings ("organelle jams" or "clogs") caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration.

False

CitationGPTRetr11260

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Abstract of the paper: Familial Alzheimer disease mutations of presenilin 1 (PS-1) enhance the generation of A beta1-42, indicating that PS-1 is involved in amyloidogenesis. However, PS-1 transgenic mice have failed to show amyloid plaques in their brains. Because PS-1 mutations facilitate apoptotic neuronal death in vitro, we did careful quantitative studies in PS-1 transgenic mice and found that neurodegeneration was significantly accelerated in mice older than 13 months (aged mice) with familial Alzheimer disease mutant PS-1, without amyloid plaque formation. However, there were significantly more neurons containing intracellularly deposited A beta42 in aged mutant transgenic mice. Our data indicate that the pathogenic role of the PS-1 mutation is upstream of the amyloid cascade.

False

CitationGPTRetr11261

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Mice as models: transgenic approaches and Alzheimer's disease. Abstract of the paper: Progress in understanding and treating Alzheimer's disease (AD) has been tremendously bolstered by the era of transgenic models of AD. The identification of disease-causing mutations in proteins such as amyloid-beta precursor protein (betaAPP) and presenilin1 (PS1), together with the discovery of other high risk factors (e.g., Apolipoprotein E4), as well as pathogenic mutations in the tau protein has led to the creation of several transgenic mice, including those expressing bi- and tri-genic constructs. Each model has unique pathologies that provide insights into disease mechanisms and interactive features of neuropathologic cascades. More importantly, therapeutic hypotheses are now testable in a manner unheard of less than 15 years ago. The wealth of new approaches currently in clinical and preclinical evaluations can be directly attributed to the impact of these animals on our ability to model relevant aspects of the disease. As a result, we may see containment or even the elimination of AD in the near future as a direct consequence of these advances.

False

CitationGPTRetr11262

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Abstract of the paper: Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. The mutant APP(K670N,M671L) transgenic line, Tg2576, shows markedly elevated amyloid beta-protein (A beta) levels at an early age and, by 9-12 months, develops extracellular AD-type A beta deposits in the cortex and hippocampus. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide A beta42(43). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M146L transgenic line develop large numbers of fibrillar A beta deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 littermates. In the period preceding overt A beta deposition, the doubly transgenic mice show a selective 41% increase in A beta42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a PS1 mutation, which causes a modest increase in A beta42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a "Y" maze before substantial A beta deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.

False

CitationGPTRetr11263

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Presenilin transgenic mice as models of Alzheimer's disease. Abstract of the paper: Mutations in presenilin-1 (PS1) and presenilin-2 (PS2) cause familial Alzheimer's disease (FAD). Presenilins influence multiple molecular pathways and are best known for their role in the gamma-secretase cleavage of type I transmembrane proteins including the amyloid precursor protein (APP). PS1 and PS2 FAD mutant transgenic mice have been generated using a variety of promoters. PS1-associated FAD mutations have also been knocked into the endogenous mouse gene. PS FAD mutant mice consistently show elevations of Abeta42 with little if any effect on Abeta40. When crossed with plaque forming APP FAD mutant lines, the PS1 FAD mutants cause earlier and more extensive plaque deposition. Although single transgenic PS1 or PS2 mice do not form plaques, they exhibit a number of pathological features including age-related neuronal and synaptic loss as well as vascular pathology. They also exhibit increased susceptibility to excitotoxic injury most likely on the basis of exaggerated calcium release from the endoplasmic reticulum. Electrophysiologically long-term potentiation in the hippocampus is increased in young PS1 FAD mutant mice but this effect appears to be lost with aging. In most studies neurogenesis in the adult hippocampus is also impaired by PS1 FAD mutants. Mice in which PS1 has been conditionally knocked out in adult forebrain on a PS2 null background (PS1/2 cDKO) develop a striking neurodegeneration that mimics AD neuropathology in being associated with neuronal and synaptic loss, astrogliosis and hyperphosphorylation of tau, although it is not accompanied by plaque deposits. The relevance of PS transgenic mice as models of AD is discussed.

False

CitationGPTRetr11264

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Accumulation of murine amyloidbeta42 in a gene-dosage-dependent manner in PS1 'knock-in' mice. Abstract of the paper: The establishment of an animal model with a missense mutation of presenilin-1 (PS1) is an initial step toward understanding the molecular pathogenesis of familial Alzheimer's disease (FAD) and developing therapeutic strategies for the disease. We previously described a Japanese family with FAD caused by the I213T mutation of PS1, in which typical signs and symptoms of Alzheimer's disease were observed at the age of 45 +/- 4.2 years [Hardy, J. (1997) Trends. Neurosci., 20, 154-159; Kamino, K et al. (1996) Neurosci. Lett., 208, 195-198]. Here, we report the establishment of 'knock-in' mice with the I213T PS1 missense mutation. Northern blot and reverse transcription polymerase chain reaction (RT-PCR) analyses showed that the mutated PS1 allele was expressed at the same level as the endogenous PS1 allele, demonstrating that the PS1 missense mutation was successfully introduced into the mouse PS1 locus, and therefore that the situation mimics that in FAD patients bearing PS1 missense mutations. Amyloid beta (Abeta) 42(43) peptide, but not Abeta40 peptide, accumulated in 'knock-in' mice at the age of 16-20 weeks. A clear gene-dosage effect on the increase of Abeta42(43) was observed in 'knock-in' mice: the percentage increase of Abeta42(43) in mice with mutations in both alleles was twice as high as that in mice with a single allele. These results indicate that the level of the mutated PS1 gene expression is likely to be critically involved in the production of highly amyloidogenic Abeta42(43), and confirm that PS1 mutation has an important effect on amyloid precursor protein (APP) processing, in proportion to the level of the expression of the mutant gene.

False

CitationGPTRetr11265

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Alzheimer disease: mouse models pave the way for therapeutic opportunities. Abstract of the paper: Research into the molecular mechanisms of Alzheimer disease (AD) continues to clarify important issues in aberrant protein processing while seeking to identify therapeutic targets. Mutations of genes on chromosomes 1, 14 (presenilins 1 and 2), and 21 (the amyloid-beta [Abeta] amyloid precursor protein [APP]) cause the familial forms of AD that often begin before age 65. An allelic polymorphism on chromosome 19 (apolipoprotein E ) affects the age of onset of the more common forms of sporadic AD. Multiple studies in transgenic mice provide strong evidence to support the view that Abeta amyloid formation is an early and critical pathogenic event: mice expressing pathogenic human APP mutations develop Abeta deposits; coexpression of mutant presenilin genes accelerates the rate of Abeta deposition; and apolipoprotein E plays a role in this process. Thus, the 3 established genetic causes or risk factors for AD affect Abeta deposition. The fact that elevation of the Abeta42/Abeta40 ratio (differing only in 2 amino acids in length) is also linked to amyloid deposition in the APP mice and is temporally linked to cognitive impairment suggests that Abeta42 may be a principal inducing factor of AD. The exact sequence of events is still unknown, but the transgenic models generated so far have shown their usefulness in clarifying this complex part of the pathology. The continuing progress in elucidation of the molecular pathogenesis of AD suggests a range of rational pharmacological interventions for this disorder. The most promising strategy involves the development of approaches to retard, halt, or prevent Abeta-mediated disease progression, and these can now be tested in transgenic animals.

False

CitationGPTRetr11266

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Overview of Transgenic Mouse Models for Alzheimer's Disease. Abstract of the paper: This review describes several transgenic mouse models of Alzheimer's disease (AD), a devastating neurodegenerative disorder that causes progressive cognitive decline and is diagnosed postmortem by the presence of extracellular amyloid-β (Aβ) plaques and intraneuronal tau neurofibrillary tangles in the cerebral cortex. Currently there is no intervention that cures, prevents, or even slows disease progression. Its complex etiology and pathology pose significant challenges for animal model development, and there is no single model that faithfully recapitulates both the pathological aspects and behavioral phenotypes of AD. Nearly 200 transgenic rodent models of AD have been generated primarily based on mutations linked to Aβ protein misprocessing in the familial form of the disease. More recent models incorporate mutations in tau protein, as well as mutations associated with the sporadic form of the disease. The salient features, strengths, limitations, and key differentiators for the most commonly used and best characterized of these models are considered here. While the translational utility of many of these models to assess the potential of novel therapeutics is in dispute, knowledge of the different models available and a detailed understanding of their features can aid in the selection of the optimal model to explore disease mechanisms or evaluate candidate medications. We comment on the predictive utility of these models considering recent clinical trial failures and discuss trends and future directions in the development of models for AD based on the plethora of clinical data that have been generated over the last decade. © 2019 by John Wiley & Sons, Inc.

False

CitationGPTRetr11267

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease. Abstract of the paper: According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L). Stereologic and image analyses revealed substantial age-related neuron loss in the hippocampal pyramidal cell layer of APP/PS-1 double-transgenic mice. The loss of neurons was observed at sites of Abeta aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques. These findings point to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer's disease.

False

CitationGPTRetr11268

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Selecting a mouse model of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disease and cause of dementia. Significant strides toward understanding and developing therapies for AD have been supported by the use of transgenic mouse models of AD. Over the last two decades, a number of mouse models have been created to recapitulate the major neuropathological hallmarks of the disease, namely amyloid plaques and neurofibrillary tangles. These mice recapitulate many, although not all, of the key features of AD, and have been widely used in AD research. At the present time, there are numerous types of transgenic mice available for the study of AD, many of which have been characterized to some extent in terms of neuronal, neuropathological, and/or behavioral abnormalities. This repository of transgenic mice offers a wealth of opportunity to investigate the cellular mechanisms underlying AD, and the choice of mouse model for research should be guided by the specific questions to be answered. We provide here some considerations for selecting a mouse model of AD best suited to particular lines of investigation.

False

CitationGPTRetr11269

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Transgenic mouse models of Alzheimer's disease. Abstract of the paper: Alzheimer's disease is the most common cause of senile dementia in the United States and Europe. At present, there is no effective treatment. Given the disease's prevalence and poor prognosis, the development of animal models has been a high research priority. Transgenic modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the amyloid precursor protein and the presenilins that cause familial forms of Alzheimer's disease. Modeling has been most aggressively pursued in mice, for which the techniques of genetic modification are well developed. Transgenic mouse models now exist that mimic a range of Alzheimer's disease-related pathologies. Although none of the models fully replicates the human disease, the models have contributed significant insights into the pathophysiology of beta-amyloid toxicity, particularly with respect to the effects of different beta-amyloid species and the possible pathogenic role of beta-amyloid oligomers. They have also been widely used in the preclinical testing of potential therapeutic modalities and have played a pivotal role in the development of immunotherapies for Alzheimer's disease that are currently in clinical trials. These models will, without a doubt, continue to play central roles in preclinical testing and be used as tools for developing insights into the biological basis of Alzheimer's disease.

False

CitationGPTRetr11270

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Transgenic Mouse Models of Alzheimer's Disease: An Integrative Analysis. Abstract of the paper: Alzheimer's disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling battery.

False

CitationGPTRetr11271

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Learning and memory in transgenic mice modeling Alzheimer's disease. Abstract of the paper: Recent advances in behavioral analyses of transgenic mouse models of Alzheimer's disease (AD) are discussed, and their impact on our understanding of the molecular basis of cognitive impairment in AD is considered. Studies of the relationship between memory and A Beta in transgenic mice expressing the amyloid precursor protein (APP) and its variants suggest that aging promotes the formation of soluble A Beta assemblies mediating negative effects on memory. A significant component of memory loss in APP transgenic mice is apparently caused by soluble A Beta assemblies, but whether and how much of the dementia within individuals afflicted with AD is caused by these A Beta species is unclear. Future studies in composite transgenic mice developing amyloid plaques, neurofibrillary tangles, and other AD pathology may allow for the determination of the relative contribution of A Beta and non-A Beta components to dementia.

False

CitationGPTRetr11272

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Abstract of the paper: Missense mutations in two related genes, termed presenilin 1 (PS1) and presenilin 2 (PS2), cause dementia in a subset of early-onset familial Alzheimer's disease (FAD) pedigrees. In a variety of experimental in vitro and in vivo settings, FAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic Abeta1-42 peptides that are preferentially deposited in the brains of Alzheimer Disease (AD) patients. In this report, we demonstrate that transgenic animals that coexpress a FAD-linked human PS1 variant (A246E) and a chimeric mouse/human APP harboring mutations linked to Swedish FAD kindreds (APP swe) develop numerous amyloid deposits much earlier than age-matched mice expressing APP swe and wild-type Hu PS1 or APP swe alone. These results provide evidence for the view that one pathogenic mechanism by which FAD-linked mutant PS1 causes AD is to accelerate the rate of beta-amyloid deposition in brain.

False

CitationGPTRetr11273

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Amyloid plaques in PSAPP mice bind less metal than plaques in human Alzheimer's disease. Abstract of the paper: Amyloid beta (Abeta) is the primary component of Alzheimer's disease (AD) plaques, a key pathological feature of the disease. Metal ions of zinc (Zn), copper (Cu), iron (Fe), and calcium (Ca) are elevated in human amyloid plaques and are thought to be involved in neurodegeneration. Transgenic mouse models of AD also exhibit amyloid plaques, but fail to exhibit the high degree of neurodegeneration observed in humans. In this study, we imaged the Zn, Cu, Fe, and Ca ion distribution in the PSAPP transgenic mouse model representing end-stage AD (N=6) using synchrotron X-ray fluorescence (XRF) microprobe. In order to account for differences in density in the plaques, the relative protein content was imaged with synchrotron Fourier transform infrared microspectroscopy (FTIRM) on the same samples. FTIRM results revealed a 61% increase in protein content in the plaques compared to the surrounding tissue. After normalizing to protein density, we found that the PSAPP plaques contained only a 29% increase in Zn and there was actually less Cu, Fe, and Ca in the plaque compared to the surrounding tissue. Since metal binding to Abeta is thought to induce redox chemistry that is toxic to neurons, the reduced metal binding in PSAPP mice is consistent with the lack of neurodegeneration in these animals. These findings were in stark contrast to the high metal ion content observed in human AD plaques, further implicating the role of metal ions in human AD pathology.

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CitationGPTRetr11274

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease. Abstract of the paper: Alzheimer's disease is characterized by the invariable accumulation of senile plaques that are predominantly composed of amyloid beta-peptide (Abeta). Abeta is generated by proteolytic processing of the beta-amyloid precursor protein (betaAPP) involving the combined action of beta- and gamma-secretase. Cleavage within the Abeta domain by alpha-secretase prevents Abeta generation. In some very rare cases of familial AD (FAD), mutations have been identified within the betaAPP gene. These mutations are located close to or at the cleavage sites of the secretases and pathologically effect betaAPP processing by increasing Abeta production, specifically its highly amyloidogenic 42 amino acid variant (Abeta42). Most of the mutations associated with FAD have been identified in the two presenilin (PS) genes, particularly the PS1 gene. Like the mutations identified within the betaAPP gene, mutations in PS1 and PS2 cause the increased generation of Abeta42. PS1 has been shown to be functionally involved in Notch signaling, a key process in cellular differentation, and in betaAPP processing. A gene knock out of PS1 in mice leads to an embryonic lethal phenotype similar to that of mice lacking Notch. In addition, absence of PS1 results in reduced gamma-secretase cleavage and leads to an accumulation of betaAPP C-terminal fragments and decreased amounts of Abeta. Recent work may suggest that PS1 could be the gamma-secretase itself, exhibiting the properties of a novel aspartyl protease. Mutagenesis of either of two highly conserved intramembraneous aspartate residues of PS1 leads to reduced Abeta production as observed in the PS1 knockout. A corresponding mutation in PS2 interfered with betaAPP processing and Notch signaling suggesting a functional redundancy of both presenilins. In this issue, some of the recent work on the molecular mechanisms involved in Alzheimer's disease (AD) as well as novel diagnostic approaches and risk factors for AD will be discussed. In the first article, we like to give an overview on mechanisms involved in the proteolytic generation of Amyloid beta-peptide (Abeta), the major pathological player of this devastating disease. In the second part of this article recent results will be described, which demonstrate an unexpected biological and pathological function of an AD associated gene.

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CitationGPTRetr11275

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: APP transgenic mice: their use and limitations. Abstract of the paper: Alzheimer's disease is the most widespread form of dementia. Its histopathological hallmarks include vascular and extracellular β-amyloid (Aβ) deposition and intraneuronal neurofibrillary tangles (NFTs). Gradual decline of cognitive functions linked to progressive synaptic loss makes patients unable to store new information in the earlier stages of the pathology, later becoming completely dependent because they are unable to do even elementary daily life actions. Although more than a hundred years have passed since Alois Alzheimer described the first case of AD, and despite many years of intense research, there are still many crucial points to be discovered in the neuropathological pathway. The development of transgenic mouse models engineered with overexpression of the amyloid precursor protein carrying familial AD mutations has been extremely useful. Transgenic mice present the hallmarks of the pathology, and histological and behavioural examination supports the amyloid hypothesis. As in human AD, extracellular Aβ deposits surrounded by activated astrocytes and microglia are typical features, together with synaptic and cognitive defects. Although animal models have been widely used, they are still being continuously developed in order to recapitulate some missing aspects of the disease. For instance, AD therapeutic agents tested in transgenic mice gave encouraging results which, however, were very disappointing in clinical trials. Neuronal cell death and NFTs typical of AD are much harder to replicate in these mice, which thus offer a fundamental but still imperfect tool for understanding and solving dementia pathology.

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CitationGPTRetr11276

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: New developments in animal models of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is characterized by deterioration in mental function leading to dementia, deposition of amyloid plaques and neurofibrillary tangles (NFTs), and neuronal loss. The major component of plaques is the amyloid-beta peptide (A beta), whereas NFTs are assemblies of hyperphosphorylated forms of the microtubule-associated protein tau. Electron microscopy of NFTs reveals structures known as paired helical filaments (PHFs). In familial AD (FAD), mutations in three distinct genes drive A beta synthesis by favoring endoproteolytic secretase cleavages that liberate A beta from the Alzheimer beta-amyloid precursor protein (APP). This suggests that excess A beta initiates a pathogenic cascade in humans that culminates in all the pathologic and cellular hallmarks of AD. Building upon the knowledge of FAD mutations, incremental technical advances have now allowed reproduceable creation of APP transgenic mice that exhibit AD-like amyloid pathology and A beta burdens. These transgenic mouse lines also exhibit deficits in spatial reference and working memory, with immunization against A beta abrogating both AD-associated phenotypes. Besides establishing a proof of principle for A beta-directed therapies, these findings suggest a potential to identify individual elements in the pathogenic pathway that lead to cognitive dysfunction. Furthermore, transgenic APP mice with potent amyloid deposition will likely form a beach-head to capture the final elements of AD neuropathology--cell loss and NFTs composed of PHFs--that are missing from current transgenic models.

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CitationGPTRetr11277

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: APP transgenic mice and their application to drug discovery. Abstract of the paper: The development of transgenic mice expressing mutated forms of the human amyloid precursor protein (APP) and presenilin-1 (PS1), proteins associated with familial forms of Alzheimer's disease (AD), has provided a backbone for translational studies of potential novel drug therapies. Such mice model some aspects of AD pathology in that they develop senile plaque-like deposits of the amyloid beta-protein (Aβ) together with inflammatory pathology and some degree of neurodegeneration. Aβ deposition is considered to be a potentially pathogenic feature of AD and drug discovery programmes utilising such mice and associated with drugs now reaching the clinic have been largely directed towards decreasing the deposition. This goal has been achieved in the mouse models, although the agents developed have not, to date, shown evidence of efficacy in AD sufferers and, in some cases, have worsened the clinical state. Nevertheless, reducing the pathological features of the disease continues to be the objective of pharmacological intervention and ongoing programmes continue to use transgenic mice expressing mutated APP and PS1 transgenes in attempts to overcome issues and difficulties arising from the initial clinical trials and to explore new approaches to AD treatment.

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CitationGPTRetr11278

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Mouse models of Alzheimer's disease for preclinical research. Abstract of the paper: Most mouse models for preclinical research into Alzheimer's disease (AD) rely on the overexpression paradigm, in which familial AD (FAD)-related genes linked to amyloid precursor protein (APP) and presenilin-1 (PSEN1) are overexpressed. Such mice have been used for over two decades as the first-generation transgenic lines for AD, with animals exhibiting AD pathologies along with additional phenotypes, leading to the serious artifacts. To overcome the intrinsic drawbacks of the overexpression paradigm, we previously developed second-generation mouse models that incorporate humanized amyloid β (Aβ) sequences and several FAD-related mutations on the mouse endogenous App gene. Such models show AD pathologies in an age-dependent manner. In addition, our group recently generated additional lines of mice harboring multiple mutations without gene overexpression; these third-generation models exhibit an accelerated AD pathology compared to earlier generations. In this review, we describe the development and future prospects of AD mouse models in terms of their scientific properties and therapeutic perspectives in the context of the preclinical study of AD.

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CitationGPTRetr11279

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: transgenic mice containing either fad ps1 or ps2 mutations show elevated levels of the relatively amyloidogenic aβ42 however these lines do not go on to develop plaques 92 93 a finding that can be explained by the fact that mice and rats lack two histidines that make up the aβ metal binding site and highlight further the potential importance of zinc dyshomeostasis mentioned earlier Title of the paper: Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Abstract of the paper: Mutations in the amyloid precursor protein (APP) gene cause early-onset familial Alzheimer disease (AD) by affecting the formation of the amyloid beta (A beta) peptide, the major constituent of AD plaques. We expressed human APP751 containing these mutations in the brains of transgenic mice. Two transgenic mouse lines develop pathological features reminiscent of AD. The degree of pathology depends on expression levels and specific mutations. A 2-fold overexpression of human APP with the Swedish double mutation at positions 670/671 combined with the V717I mutation causes A beta deposition in neocortex and hippocampus of 18-month-old transgenic mice. The deposits are mostly of the diffuse type; however, some congophilic plaques can be detected. In mice with 7-fold overexpression of human APP harboring the Swedish mutation alone, typical plaques appear at 6 months, which increase with age and are Congo Red-positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. The immunoreactivity is exclusively found in congophilic senile plaques of both lines. In the higher expressing line, elevated tau phosphorylation can be demonstrated biochemically in 6-month-old animals and increases with age. These mice resemble major features of AD pathology and suggest a central role of A beta in the pathogenesis of the disease.

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CitationGPTRetr11280

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Fitness effects on the cognitive function of older adults: a meta-analytic study. Abstract of the paper: A meta-analytic study was conducted to examine the hypothesis that aerobic fitness training enhances the cognitive vitality of healthy but sedentary older adults. Eighteen intervention studies published between 1966 and 2001 were entered into the analysis. Several theoretically and practically important results were obtained. Most important fitness training was found to have robust but selective benefits for cognition, with the largest fitness-induced benefits occurring for executive-control processes. The magnitude of fitness effects on cognition was also moderated by a number of programmatic and methodological factors, including the length of the fitness-training intervention, the type of the intervention, the duration of training sessions, and the gender of the study participants. The results are discussed in terms of recent neuroscientific and psychological data that indicate cognitive and neural plasticity is maintained throughout the life span.

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CitationGPTRetr11281

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. Abstract of the paper: Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

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CitationGPTRetr11282

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Improving aerobic capacity in healthy older adults does not necessarily lead to improved cognitive performance. Abstract of the paper: The effects of aerobic exercise training in a sample of 85 older adults were investigated. Ss were assigned randomly to either an aerobic exercise group, a nonaerobic exercise (yoga) group, or a waiting-list control group. Following 16 weeks of the group-specific protocol, all of the older Ss received 16 weeks of aerobic exercise training. The older adults demonstrated a significant increase in aerobic capacity (cardiorespiratory fitness). Performance on reaction-time tests of attention and memory retrieval was slower for the older adults than for a comparison group of 24 young adults, and there was no improvement in the older adults' performance on these tests as a function of aerobic exercise training. Results suggest that exercise-related changes in older adults' cognitive performance are due either to extended periods of training or to cohort differences between physically active and sedentary individuals.

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CitationGPTRetr11283

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Enhancing brain and cognitive function of older adults through fitness training. Abstract of the paper: The present article provides a brief review of the human and animal literature that has investigated the relationship between fitness training and brain and cognitive function. The animal research clearly suggests that improvements in fitness can lead to both morphological and functional changes in the brains of older animals. Results of a recent meta-analysis suggest that fitness training can also have beneficial effects on human cognition, particularly on tasks requiring executive control processing. These effects are also moderated by a number of factors, including the proportion of men and women in the intervention studies, the length of training sessions, the age of the participants, and the combination of fitness training regimes. The article also discusses preliminary results that link, for the first time, fitness training and differences in human brain structure and function. Finally, we discuss the important issue of participant adherence to fitness training programs and the factors that influence fitness participation.

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CitationGPTRetr11284

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Cognitive and physical factors affecting daily function in Alzheimer's disease: A cross-sectional analysis. Abstract of the paper: Understanding the factors affecting activities of daily living (ADL) is important in Alzheimer's disease (AD), because decline in ADL contributes to many poor health outcomes. Existing studies often investigate the factors in isolation without a theoretical framework. The purpose of the present study was to provide preliminary results on how cognition, physical performance, and behavioral and psychological symptoms of dementia mediate the relationship of aerobic fitness and ADL in AD. A cross-sectional analysis was used (n = 28: average age 78 [8] years, education 16 (3) years, Mini-Mental State Examination scores 20 [4]). The results showed that aerobic fitness is not linked to ADL directly, and its association with ADL was mediated by physical performance and global cognition. Our findings provide preliminary support for aerobic fitness as a potential therapeutic target, as enhanced aerobic fitness could simultaneously modify other factors affecting ADL. Nurses are in a unique position for coordinating exercise safety assessment and prescription and educating older adults with AD about exercise participation.

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CitationGPTRetr11285

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Effects of cardiorespiratory fitness and cerebral blood flow on cognitive outcomes in older women. Abstract of the paper: The mechanisms by which aerobic fitness confers beneficial effects on cognition with aging are unclear but may involve cerebrovascular adaptations. In a cross-sectional study of women from the community (n=42; age range=50-90 years), we sought to determine whether physical fitness is associated with higher cerebrovascular function, and its relationship to cognition. Main outcome measures included resting cerebral blood flow, cerebrovascular reserve, physical fitness (i.e., VO₂max) and cognition. Physically fit women had lower resting mean arterial pressure (MAP) and higher cerebrovascular conductance (CVC) than sedentary women. Overall cognition was negatively correlated with age and positively correlated with VO₂max. VO₂max was a predictor of resting CVC and MAP, and CVC and MAP when end-tidal gases were held constant at near-resting values. MAP and CVC were predictors of cognition. This study identified strong associations between physical fitness, vascular function and cognition, and provides new understanding regarding the mechanisms by which fitness positively impacts cognition with aging. The implications of this research are considerable and warrant future investigation.

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CitationGPTRetr11286

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Aerobic exercise to improve cognitive function in older people without known cognitive impairment. Abstract of the paper: BACKGROUND There is increasing evidence that physical activity supports healthy ageing. Exercise is helpful for cardiovascular, respiratory and musculoskeletal systems, among others. Aerobic activity, in particular, improves cardiovascular fitness and, based on recently reported findings, may also have beneficial effects on cognition among older people. OBJECTIVES To assess the effect of aerobic physical activity, aimed at improving cardiorespiratory fitness, on cognitive function in older people without known cognitive impairment. SEARCH METHODS We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, the Cochrane Controlled Trials Register (CENTRAL) (all years to Issue 2 of 4, 2013), MEDLINE (Ovid SP 1946 to August 2013), EMBASE (Ovid SP 1974 to August 2013), PEDro, SPORTDiscus, Web of Science, PsycINFO (Ovid SP 1806 to August 2013), CINAHL (all dates to August 2013), LILACS (all dates to August 2013), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch), ClinicalTrials.gov (https://clinicaltrials.gov) and Dissertation Abstracts International (DAI) up to 24 August 2013, with no language restrictions. SELECTION CRITERIA We included all published randomised controlled trials (RCTs) comparing the effect on cognitive function of aerobic physical activity programmes with any other active intervention, or no intervention, in cognitively healthy participants aged over 55 years. DATA COLLECTION AND ANALYSIS Two review authors independently extracted the data from included trials. We grouped cognitive outcome measures into eleven categories covering attention, memory, perception, executive functions, cognitive inhibition, cognitive speed and motor function. We used the mean difference (or standardised mean difference) between groups as the measure of the treatment effect and synthesised data using a random-effects model. We conducted separate analyses to compare aerobic exercise interventions with no intervention and with other exercise, social or cognitive interventions. Also, we performed analyses including only trials in which an increase in the cardiovascular fitness of participants had been demonstrated. MAIN RESULTS Twelve trials including 754 participants met our inclusion criteria. Trials were from eight to 26 weeks in duration.We judged all trials to be at moderate or high risk of bias in at least some domains. Reporting of some risk of bias domains was poor.Our analyses comparing aerobic exercise to any active intervention showed no evidence of benefit from aerobic exercise in any cognitive domain. This was also true of our analyses comparing aerobic exercise to no intervention. Analysing only the subgroup of trials in which cardiorespiratory fitness improved in the aerobic exercise group showed that this improvement did not coincide with improvements in any cognitive domains assessed. Our subgroup analyses of aerobic exercise versus flexibility or balance interventions also showed no benefit of aerobic exercise in any cognitive domain.Dropout rates did not differ between aerobic exercise and control groups. No trial reported on adverse effects.Overall none of our analyses showed a cognitive benefit from aerobic exercise even when the intervention was shown to lead to improved cardiorespiratory fitness. AUTHORS' CONCLUSIONS We found no evidence in the available data from RCTs that aerobic physical activities, including those which successfully improve cardiorespiratory fitness, have any cognitive benefit in cognitively healthy older adults. Larger studies examining possible moderators are needed to confirm whether or not aerobic training improves cognition.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Aerobic physical activity to improve memory and executive function in sedentary adults without cognitive impairment: A systematic review and meta-analysis. Abstract of the paper: The worldwide population of adults ages 50 and older continues to increase and is projected to reach over 2.3 billion by 2030. Aging is the biggest risk factor for cognitive impairment and dementia. Aerobic physical activity may improve cognitive functioning, thus delaying aging-related cognitive decline. The purpose of this review was to examine the effect of aerobic physical activity on memory and executive function in sedentary adults with no known cognitive impairment. PubMed, CINAHL, Psycinfo, and Cochrane Library databases were systematically searched for peer-reviewed articles up to July 2019. Randomized controlled trials of sedentary adults, aged 50 and older, that compared an aerobic physical activity intervention to either no treatment or alternative active comparator and reported outcome measures of memory and/or executive function were included. A random effects meta-analysis was performed to examine the separate effect sizes for memory and executive function. Nine studies met inclusion criteria and contributed either memory and/or executive function effect sizes (n = 547). Results from the random effects meta-analysis suggested, by post-intervention, a large effect size for the aerobic physical activity interventions on memory (g = 0.80, 95%CI: 0.14-1.47; n = 7; p = 0.02) and a small effect on executive function (g = 0.37, 95%CI: 0.04-0.69; n = 6; p = 0.03). Aerobic physical activity may improve memory and executive function in sedentary adults without cognitive impairment. Policymakers and providers should promote aerobic physical activity in this population, and further research should investigate the most effective ways to promote aerobic physical activity in mid-life to older adults.

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CitationGPTRetr11288

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial. Abstract of the paper: BACKGROUND There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer's disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. METHODS AND FINDINGS This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control intervention in individuals with early AD. A total of 76 well-characterized older adults with probable AD (mean age 72.9 [7.7]) were enrolled and 68 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. Neuropsychological tests and surveys were conducted at baseline,13, and 26 weeks to assess memory and executive function composite scores, functional ability (Disability Assessment for Dementia), and depressive symptoms (Cornell Scale for Depression in Dementia). Cardiorespiratory fitness testing and brain MRI was performed at baseline and 26 weeks. Aerobic exercise was associated with a modest gain in functional ability (Disability Assessment for Dementia) compared to individuals in the ST group (X2 = 8.2, p = 0.02). There was no clear effect of intervention on other primary outcome measures of Memory, Executive Function, or depressive symptoms. However, secondary analyses revealed that change in cardiorespiratory fitness was positively correlated with change in memory performance and bilateral hippocampal volume. CONCLUSIONS Aerobic exercise in early AD is associated with benefits in functional ability. Exercise-related gains in cardiorespiratory fitness were associated with improved memory performance and reduced hippocampal atrophy, suggesting cardiorespiratory fitness gains may be important in driving brain benefits. TRIAL REGISTRATION ClinicalTrials.gov NCT01128361.

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CitationGPTRetr11289

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise. Abstract of the paper: Alzheimer disease (AD) and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Aerobic exercise effects upon cognition in Mild Cognitive Impairment: A systematic review of randomized controlled trials. Abstract of the paper: Several studies have shown that physical activity has positive effects on cognition in healthy older adults without cognitive complains but lesser is known about the effectiveness of aerobic exercise in patients suffering from Mild Cognitive Impairment (MCI). The aim of the present study was to systematically review the evidence from randomized controlled trials (RCTs) about the effects of aerobic exercise upon cognition in MCI patients. To this end, PubMed, Cochrane and Web of Science databases were analytically searched for RCTs including aerobic exercise interventions for MCI patients. There is evidence that aerobic exercise improves cognition in MCI patients. Overall research reported moderate effects for global cognition, logical memory, inhibitory control and divided attention. Due to methodological limitations of the investigated studies, findings should be interpreted with caution. Standardized training protocols, larger scale interventions and follow-ups may also provide better insight into the preventive effects of aerobic exercise on cognitive deterioration in MCI and its conversion into dementia.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly. Abstract of the paper: Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

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CitationGPTRetr11292

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Abstract of the paper: Physical exercise, particularly aerobic exercise, is documented as providing a low cost regimen to counter well-documented cognitive declines including memory, executive function, visuospatial skills, and processing speed in normally aging adults. Prior aging studies focused largely on the effects of medium to long term (>6 months) exercise training; however, the shorter term effects have not been studied. In the present study, we examined changes in brain blood flow, cognition, and fitness in 37 cognitively healthy sedentary adults (57-75 years of age) who were randomized into physical training or a wait-list control group. The physical training group received supervised aerobic exercise for 3 sessions per week 1 h each for 12 weeks. Participants' cognitive, cardiovascular fitness and resting cerebral blood flow (CBF) were assessed at baseline (T1), mid (T2), and post-training (T3). We found higher resting CBF in the anterior cingulate region in the physical training group as compared to the control group from T1 to T3. Cognitive gains were manifested in the exercise group's improved immediate and delayed memory performance from T1 to T3 which also showed a significant positive association with increases in both left and right hippocampal CBF identified earlier in the time course at T2. Additionally, the two cardiovascular parameters, VO2 max and rating of perceived exertion (RPE) showed gains, compared to the control group. These data suggest that even shorter term aerobic exercise can facilitate neuroplasticity to reduce both the biological and cognitive consequences of aging to benefit brain health in sedentary adults.

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CitationGPTRetr11293

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Facilitating aerobic exercise training in older adults with Alzheimer's disease. Abstract of the paper: Emerging science suggests that aerobic exercise might modify the pathophysiology of Alzheimer's disease (AD) and improve cognition. However, there are no clinical practice guidelines for aerobic exercise prescription and training in older adults with AD. A few existing studies showed that older adults with AD can participate in aerobic exercise and improve dementia symptoms, but lack adequate descriptions of their aerobic exercise training programs and their clinical applicability. In this paper, we summarize current knowledge about the potential benefits of aerobic exercise in older adults with AD. We then describe the development of a moderate-intensity aerobic exercise program for this population and report results from its initial testing in a feasibility trial completed by two persons with AD. Two older adults with AD completed the aerobic exercise program. Barriers to the program's implementation are described, and methods to improve more wide-spread adoption of such programs and the design of future studies that test them are suggested.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Exercise Improves Vascular Function, but does this Translate to the Brain? Abstract of the paper: The number of adults with Alzheimer's disease (AD) or related dementia is expected to increase exponentially. Interventions aimed to reduce the risk and progression of AD and dementia are critical to the prevention and treatment of this devastating disease. Aging and cardiovascular disease risk factors are associated with reduced vascular function, which can have important clinical implications, including brain health. The age-associated increase in blood pressure and impairment in vascular function may be attenuated or even reversed through lifestyle behaviors. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on vascular health and cognition. Exercise and cardiorespiratory fitness may be most important during midlife, as physical activity and cardiorespiratory fitness during the middle-aged years are associated with future cognitive function. The extent to which exercise, and more specifically aerobic exercise, influences the cerebral circulation is not well established. In this review, we present our working hypothesis showing how cerebrovascular function may be a mediating factor underlying the association between exercise and cognition, as well as discuss recent studies evaluating the effect of exercise interventions on the cerebral circulation.

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CitationGPTRetr11295

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Physical activity, fitness, and gray matter volume. Abstract of the paper: In this review, we explore the association among physical activity, cardiorespiratory fitness, and exercise on gray matter volume in older adults. We conclude that higher cardiorespiratory fitness levels are routinely associated with greater gray matter volume in the prefrontal cortex and hippocampus and less consistently in other regions. We also conclude that physical activity is associated with greater gray matter volume in the same regions that are associated with cardiorespiratory fitness including the prefrontal cortex and hippocampus. Some heterogeneity in the literature may be explained by effect moderation by age, stress, or other factors. Finally, we report promising results from randomized exercise interventions that suggest that the volume of the hippocampus and prefrontal cortex remain pliable and responsive to moderate intensity exercise for 6 months-1 year. Physical activity appears to be a propitious method for influencing gray matter volume in late adulthood, but additional well-controlled studies are necessary to inform public policies about the potential protective or therapeutic effects of exercise on brain volume.

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CitationGPTRetr11296

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Cardiorespiratory fitness is associated with atrophy in Alzheimer's and aging over 2 years. Abstract of the paper: We sought to describe change in cardiorespiratory (CR) fitness over 2 years in those with early-stage Alzheimer's disease (AD) and nondemented aging and assess the relationship of CR fitness with cognitive decline, brain atrophy, and dementia progression. Individuals with early-stage AD (n = 37) and without dementia (n = 53) attended clinical evaluations, cognitive and exercise tests, and magnetic resonance imaging (MRI) at baseline and 2 years later. CR fitness was lower in those with AD over the study period. Lower baseline CR fitness was associated with progression of dementia severity in AD. Declining CR fitness over 2 years was associated with brain atrophy in AD, especially in the parahippocampus. In nondemented participants, there was a trend for lower baseline fitness to be related to cognitive decline. Both lower baseline CR fitness and declining CR fitness over 2 years were associated with regional brain atrophy. We conclude that CR fitness is chronically reduced in those with AD. Further, in those with AD, CR fitness is associated with progression of dementia severity and brain atrophy in AD, suggesting a link between progression of dementia severity and cardiorespiratory health.

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CitationGPTRetr11297

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Exercise, cognition, and the aging brain. Abstract of the paper: We provide a brief review of the literature on exercise effects on brain and cognition. To this end, we focus on both prospective and retrospective human epidemiological studies that have examined the influence of exercise and physical activity on cognition and dementia. We then examine the relatively small set of human randomized clinical trials that have, for the most part, focused on exercise training effects on cognition. Next, we discuss animal research that has examined the molecular, cellular, and behavioral effects of exercise training. Finally, we conclude with a summary and brief discussion of important future directions of research on fitness cognition and brain.

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CitationGPTRetr11298

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Improving cognition and function through exercise intervention in Alzheimer's disease. Abstract of the paper: PURPOSE To analyze the effects of cognition on function and to explore the potential of aerobic exercise for promoting cognitive and functional capacities. DESIGN Integrative review of literature. METHODS Studies were selected based on an extensive search of electronic databases and manual cross-referencing for 1980 to 2006, using the combination of key words: Alzheimer's disease (AD), dementia, or cognitive impairment with function or activities of daily living. FINDINGS Three broad themes were identified from the literature analysis. First, global cognition has mainly been used to examine the effect of cognition on function, indicating an assumption that functional decline progresses in a hierarchical manner in AD. Second, specific cognitive domains affect functional decline in different ways. Executive functioning might have more effect on function than does memory. Third, aerobic exercise might promote cognitive and functional capacities in people with AD by modifying neuropathological changes in the brain. CONCLUSIONS Specific cognitive domains such as executive functioning are important for understanding function in people with AD and are potentially modifiable by aerobic exercise.

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CitationGPTRetr11299

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: crosssectional and few prospective studies in predominantly normal whites samples suggested that aerobic fitness can enhance cognitive function Title of the paper: Affecting cognition and quality of life via aerobic exercise in Alzheimer's disease. Abstract of the paper: Aerobic exercise is a promising behavioral therapy for Alzheimer's disease (AD), yet few studies have investigated the effect of aerobic exercise on cognition in AD. The purpose of this pilot study was to examine the effect of 6-month aerobic exercise on the change in executive function, global cognition, quality of life (QOL), and depression in community-dwelling older adults with mild to moderate AD. A single group, repeated measures design with outcomes measured at baseline, 3 months, and 6 months was used. Results show that there were no significant changes in any measures except for depression (p = .026). There was a trend toward improvement in executive function and QOL with moderate effect sizes (ESs) and a trend toward deterioration in global cognition with moderate to large ESs. Randomized controlled trials are needed to evaluate the therapeutic effect of aerobic exercise in older adults with AD.

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