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CitationGPTRetr800

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epileptic activity in Alzheimer's disease: causes and clinical relevance. Abstract of the paper: Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer's disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer's disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer's disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.

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CitationGPTRetr801

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Seizures in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies.

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CitationGPTRetr802

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: The overlap between epilepsy and Alzheimer's disease and the consequences for treatment. Abstract of the paper: Introduction: Alzheimer's disease may be associated with both clinical and subclinical epileptic seizure activity. Once regarded as an epiphenomenon, epileptiform activity may, in fact, be an integral part of the Alzheimer's phenotype, and may be not only a symptomatic therapeutic target but also a possible mechanism to retard or prevent disease progression. Areas covered: The authors review clinical research articles with a focus on the semiology, epidemiology, and treatment of seizures in Alzheimer's disease, and also look at some experimental animal model studies which have informed clinical thinking on seizure aetiopathogenesis. The evidence base for treatment decisions is sparse. A brief overview of the clinical assessment of Alzheimer's disease patients considering relevant differential diagnoses and diagnostic pitfalls is presented. Expert opinion: Studies of epileptic seizures in Alzheimer's disease have become more frequent over the last 5-10 years. Understanding of seizure semiology, epidemiology, and possible pathogenesis has increased. However, the optimal management of seizures in this context remains unknown, largely due to the paucity of studies sufficient to examine this question. Clearly, such studies will be required, not only to inform clinicians about symptomatic control of seizures in Alzheimer's disease but also to investigate whether this might impact on disease progression.

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CitationGPTRetr803

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epileptic Seizures in Alzheimer Disease: A Review. Abstract of the paper: Alzheimer disease (AD) is the most frequent cause of major neurocognitive disorders with a huge economical and medical burden. Several studies pointed out that AD is associated with a high risk for developing epileptic seizures. The aims of our review were to evaluate and to summarize the current literature (ending in September 2015) of animal and human studies in the relation of AD and epileptic seizures. It seems likely that epileptic hyperexcitation could be partially responsible for the progression of AD due to the increased rate of amyloid deposition. Pathologic changes in animal models of AD are similar to those seen in human temporal lobe epilepsy. Antiepileptic treatment had a positive effect on cognitive function in animal and human studies. Because the detection of seizures in patients with cognitive decline is extremely difficult because of methodological problems, the true prevalence of seizures has remained unclear. Nonconvulsive seizures with no overt clinical symptoms may be frequent seizure types in AD. These are difficult to detect by clinical observation and with standard scalp electroencephalogram (EEG) methods. We propose that long-term EEG recording and video-EEG monitoring is necessary to prove the presence of epileptiform activity in demented patients.

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CitationGPTRetr804

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epilepsy in patients with Alzheimer's disease: A systematic review. Abstract of the paper: Alzheimer's disease (AD) and epilepsy are common disorders in the elderly. Evidence demonstrates that patients with AD have an increased risk of developing epilepsy and seizures. OBJECTIVE To review epidemiological, clinical and treatment aspects of epilepsy and AD. METHODS We reviewed databases (PubMED, LiLACS, Scielo) conducting a search for manuscripts using the terms Alzheimer's disease and epilepsy. RESULTS Manuscripts related to the areas of interest were reviewed. Studies revealed that epilepsy is more frequent among AD patients. The combined presence of the two disorders may be related to mechanisms of neuronal hyperexcitability as a consequence of amyloid-beta protein (Aβ) or phosphorylated tau accumulation, as well as to structural changes in cortical and hippocampal regions. Available data suggest that the new generation of antiepileptic drugs (AEDs) are better tolerated in the elderly population, and may also be the best option in patients with AD and epilepsy. CONCLUSION Further prospective studies involving evaluation of concomitant dementia and epilepsy, neurophysiological findings and biomarkers need to be performed.

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CitationGPTRetr805

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Alzheimer's disease and epilepsy: An increasingly recognized comorbidity. Abstract of the paper: Both Alzheimer's disease (AD) and epilepsy are common chronic diseases in older people. Seizures and epileptiform discharges are very prevalent in AD and can occur since any stage of AD. Increasing evidence indicates that AD and epilepsy may be comorbid. Several factors may be related to the underlying mechanism of the comorbidity. Identifying seizures in patients with AD is a challenge because seizures are often clinically non-motor and may overlap with some AD symptoms. Not only seizures but also epileptiform discharges may exacerbate the cognitive decline in AD patients, highlighting the importance of early recognition and treatment. This review provides a comprehensive overview of seizures in AD from multiple aspects to provide more insight.

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CitationGPTRetr806

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epilepsy and Alzheimer's Disease: Potential mechanisms for an association. Abstract of the paper: Alzheimer's Disease (AD) and epilepsy are common neurological diseases. The prevalence of epilepsy in AD patients is higher than in healthy subjects, but identifying the reasons for this association, the characteristics of seizures in AD, and the implications for prognosis and treatment is challenging. The present review provides first of all an overview of the main clinical aspects of AD and epilepsy, of their reciprocal relationship, and of the challenges that identifying seizures in AD patients presents. Limitations of clinical studies addressing this topic are discussed, including their mostly prospective nature and possible selection biases. A comprehensive, mechanistic discussion on the factors that are most likely to underlie the increased risk for seizures in AD follows. These include, for instance, GABAergic and glutamatergic alterations, Aβ and Tau protein, the role of the noradrenergic nucleus Locus Coeruleus, and neuroinflammation. Finally, evidence concerning the role that epilepsy may have in exacerbating or initiating AD is reviewed. A mechanistic insight on the relationship between epilepsy and AD might have relevant implications for improving the treatment of AD patients, as well as in elucidating pathophysiological mechanisms.

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CitationGPTRetr807

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Alzheimer's Disease and Epilepsy: A Perspective on the Opportunities for Overlapping Therapeutic Innovation. Abstract of the paper: Early-onset Alzheimer's disease (AD) is associated with variants in amyloid precursor protein (APP) and presenilin (PSEN) 1 and 2. It is increasingly recognized that patients with AD experience undiagnosed focal seizures. These AD patients with reported seizures may have worsened disease trajectory. Seizures in epilepsy can also lead to cognitive deficits, neuroinflammation, and neurodegeneration. Epilepsy is roughly three times more common in individuals aged 65 and older. Due to the numerous available antiseizure drugs (ASDs), treatment of seizures has been proposed to reduce the burden of AD. More work is needed to establish the functional impact of seizures in AD to determine whether ASDs could be a rational therapeutic strategy. The efficacy of ASDs in aged animals is not routinely studied, despite the fact that the elderly represents the fastest growing demographic with epilepsy. This leaves a particular gap in understanding the discrete pathophysiological overlap between hyperexcitability and aging, and AD more specifically. Most of our preclinical knowledge of hyperexcitability in AD has come from mouse models that overexpress APP. While these studies have been invaluable, other drivers underlie AD, e.g. PSEN2. A diversity of animal models should be more frequently integrated into the study of hyperexcitability in AD, which could be particularly beneficial to identify novel therapies. Specifically, AD-associated risk genes, in particular PSENs, altogether represent underexplored contributors to hyperexcitability. This review assesses the available studies of ASDs administration in clinical AD populations and preclinical studies with AD-associated models and offers a perspective on the opportunities for further therapeutic innovation.

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CitationGPTRetr808

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Seizures and epilepsy in Alzheimer's disease. Abstract of the paper: Many studies have shown that patients with Alzheimer's disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome, and progression vary widely between studies. We performed a literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG) studies, and treatment responses. Finally, we consider limitations and methodological issues. There is considerable variability in the reported prevalence and incidence of seizures in patients with AD-with reported lifetime prevalence rates of 1.5-64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps.

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CitationGPTRetr809

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Seizures in Alzheimer disease: clinical and epidemiological data. Abstract of the paper: Alzheimer disease (AD) and epilepsy are disorders commonly seen in the elderly. Many studies have shown that patients with AD are at increased risk for developing seizures and epilepsy. Whereas, patients with specific types of epilepsy, such as temporal lobe epilepsy (TLE), experience some degree of cognitive dysfunction, questions have been raised as to whether these disorders share some underlying pathophysiologic mechanisms or whether one is an epiphenomenon of the other. In this report, we review some of the available clinical and epidemiologic literature on various aspects of the topic of seizures in AD, including seizure rates and types, risk factors for seizures, electroencephalographic findings, treatment options, limitations, and methodological issues. Overall, multiple aspects of the literature on seizures and epilepsy in AD, including diagnosis, risk factors, the role of EEG in diagnosis, and the response to treatment are not clear and suffer from many methodological limitations and gaps.

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CitationGPTRetr810

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epilepsy and Alzheimer's Disease: Current Concepts and Treatment Perspective on Two Closely Related Pathologies. Abstract of the paper: The literature on epileptic seizures in Alzheimer's disease has significantly increased over the past decades. Remarkably, several studies suggest a bi-directional link between these two common neurological diseases, with either condition carrying a nearly 2-fold risk of contracting the other in comparison to healthy subjects. In this respect, evidence from both clinical and preclinical studies indicates that epileptogenesis and neurodegeneration possibly share common underlying mechanisms. However, the precise association between epileptogenesis and neurodegeneration still needs to be fully elucidated. Targeted intervention to reduce abnormal network hyperexcitability might constitute a therapeutic strategy to postpone the onset of later neurodegenerative changes and consequent cognitive decline by many years in patients. By virtue of this, an early diagnosis and treatment of seizures in patients with Alzheimer's disease should be pursued. To date, no guidelines are available for treating epileptic activity in this context, largely due to the paucity of studies sufficient to answer the related questions. Accordingly, clinical trials are mandatory, not only to inform clinicians about symptomatic management of seizures in Alzheimer's disease patients but also to detect if treatment with antiseizure medications could have disease-modifying effects. Moreover, it will be fundamental to expand the application of animal models of Alzheimer's disease to comorbid conditions, such as epilepsy both to reveal the mechanisms underlying seizure onset and to better define their role in cognitive decline. Such models could also be useful to identify pharmacological compounds having therapeutically effectiveness as well as reliable early biomarkers for seizures in Alzheimer's disease.

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CitationGPTRetr811

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Recommendations for Preclinical Testing of Treatments Against Alzheimer's Disease-Related Epileptiform Spikes in Transgenic Rodent Models. Abstract of the paper: Recent evidence suggests that about 30%of patients with mild to moderate Alzheimer's disease (AD) without a known diagnosis of epilepsy may display epileptiform spikes during electroencephalographic (EEG) recordings. These abnormal discharges occur predominantly during sleep and may be associated with accelerated disease progression. Subclinical spikes may represent a relevant target for clinical drug interventions, and there is a clear unmet need for preclinical testing of novel disease modifying agents in suitable animal models. Transgenic rodent models of AD pathology exhibit various forms of epileptiform EEG activity related to the abnormal levels of amyloid species in the brain. Among them, large-amplitude cortical and hippocampal EEG spikes in mouse and rat AD models may be reminiscent of the subclinical epileptiform EEG spikes recorded in some AD patients. This article reports the recommendations of a multidisciplinary panel of experts on optimal EEG markers and experimental designs to measure and report epileptiform activities and their response to symptomatic and disease-modifying drugs in transgenic AD model rodents. These recommendations may harmonize future preclinical EEG studies in the drug discovery research and may increase the comparability of experimental outcomes and their translational clinical value.

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CitationGPTRetr812

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epilepsy and cognitive impairments in Alzheimer disease. Abstract of the paper: Alzheimer disease (AD) is associated with cognitive decline and increased incidence of seizures. Seizure activity in AD has been widely interpreted as a secondary process resulting from advanced stages of neurodegeneration, perhaps in combination with other age-related factors. However, recent findings in animal models of AD have challenged this notion, raising the possibility that aberrant excitatory neuronal activity represents a primary upstream mechanism that may contribute to cognitive deficits in these models. The following observations suggest that such activity may play a similar role in humans with AD: (1) patients with sporadic AD have an increased incidence of seizures that appears to be independent of disease stage and highest in cases with early onset; (2) seizures are part of the natural history of many pedigrees with autosomal dominant early-onset AD, including those with mutations in presenilin-1, presenilin-2, or the amyloid precursor protein, or with duplications of wild-type amyloid precursor protein; (3) inheritance of the major known genetic risk factor for AD, apolipoprotein E4, is associated with subclinical epileptiform activity in carriers without dementia; and (4) some cases of episodic amnestic wandering and disorientation in AD are associated with epileptiform activity and can be prevented with antiepileptic drugs. Here we review recent experimental data demonstrating that high levels of beta-amyloid in the brain can cause epileptiform activity and cognitive deficits in transgenic mouse models of AD. We conclude that beta-amyloid peptides may contribute to cognitive decline in AD by eliciting similar aberrant neuronal activity in humans and discuss potential clinical and therapeutic implications of this hypothesis.

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CitationGPTRetr813

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: [Alzheimer's disease and epilepsy]. Abstract of the paper: Data regarding the incidence and prevalence of epileptic seizures in Alzheimer's disease show great variability and are clinically underestimated due to their atypical symptomatology. Considering their considerable negative effects on cognition and activities of daily living, epileptic seizures need to be correctly treated. Hypotheses with respect to the pathogenetic mechanisms and associations between Alzheimer's disease and epilepsy are mostly derived from animal experiments. The causal connections are so far insufficiently understood. Data on risk factors are inconsistent due to methodological limitations in studies. Clinical data for these indications show good response to therapy with anticonvulsants and good tolerability in the case of new active substances. When treating epileptic seizures in this patient collective using anticonvulsants, potential adverse effects and possible drug interactions need to be closely monitored.

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CitationGPTRetr814

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Epileptic seizures in AD patients. Abstract of the paper: Epileptic seizures have long been recognised as a complication of the clinical syndrome of Alzheimer's disease, particularly in advanced disease, but have hitherto been viewed essentially as epiphenomena of the neurodegenerative process. Progress with animal models of Alzheimer's disease has suggested that this view may be incorrect, and that seizures may be a reflection of pathophysiological processes similar to or overlapping with those responsible for cognitive decline. This overlap between neuropsychological and neurophysiological changes suggests that seizures in Alzheimer's disease may be a valid therapeutic target, over and above symptomatic treatment. This article reviews data on the prevalence of seizures in Alzheimer's disease, seizure types, pathophysiology and treatment. Seizure prevalence increases with disease duration, but early-onset disease is associated with a greater risk of seizures, in part related to the frequency of presenilin-1 gene mutations in early-onset disease. Seizures are mostly of partial origin, with both complex partial and secondary generalised seizures. Seizure pathophysiology may relate to increased amyloid beta-peptide production, structural alterations in neurones related to cytoskeletal dysfunction, cerebrovascular changes, neurotransmitter dysfunction or combinations thereof. Through modification of these pathophysiological pathways, there may be possible roles for anti-epileptic drugs such as sodium valproate and lacosamide in the treatment of Alzheimer's disease. In summary, epileptic seizures are part of the AD phenotype, and merit further investigation.

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CitationGPTRetr815

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Subclinical epileptiform activity accelerates the progression of Alzheimer's disease: A long-term EEG study. Abstract of the paper: OBJECTIVE While many studies suggest that patients with Alzheimer's disease have a higher chance for developing epileptic seizures, only a few studies are available examining independent epileptic discharges. The major aims of our study was to determine the prevalence of subclinical epileptiform activity (SEA) in AD compared to healthy elderly controls with the hypothesis that SEA is more frequent in AD than in cognitively normal individuals. Another aim was to analyze the effect of baseline SEA captured with electroencephalography on the progression of the disease with longitudinal cognitive testing. METHODS We investigated 52 Alzheimer patients with no history of epileptic seizures and 20 healthy individuals. All participants underwent a 24-hour electroencephalography, neurology, neuroimaging and neuropsychology examination. Two independent raters analyzed visually the electroencephalograms and both raters were blind to the diagnoses. Thirty-eight Alzheimer patients were enrolled in a 3-year long prospective follow-up study with yearly repeated cognitive evaluation. RESULTS Subclinical epileptiform discharges were recorded significantly (p:0.018) more frequently in Alzheimer patients (54%) than in healthy elderly (25%). Epileptiform discharges were associated with lower performance scores in memory. Alzheimer patients with spikes showed 1.5-times faster decline in global cognitive scores than patients without (p < 0.001). The decline in cognitive performance scores showed a significant positive correlation with spike frequency (r:+0.664; p < 0.001). CONCLUSIONS Subclinical epileptiform activity occurs in half of Alzheimer patients who have never suffered epileptic seizures. Alzheimer patients with subclinical epileptiform activity showed accelerated cognitive decline with a strong relation to the frequency and spatial distribution (left temporal) of spikes. SIGNIFICANCE Our findings suggest the prominent role of epileptiform discharges in the pathomechanism of Alzheimer's disease which might serve as potential therapeutic target.

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CitationGPTRetr816

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Seizure in Alzheimer's Disease: An Underestimated Phenomenon. Abstract of the paper: Alzheimer's disease (AD) is considered as a potential risk factor for the development of seizure due to neurodegeneration and imbalance between stimulatory and inhibitory circuits in the brain. Seizure could occur in any point during the course of AD, and its presentation varies from fluctuation in cognitive domains to more typical seizures. The clinical diagnosis of seizure in patients with dementia may be challenging due to difficulty in history taking and clinical assessment. No paraclinic methods other than electroencephalogram (EEG) could provide arguments for the diagnosis of AD-related seizures (neither imaging modalities nor cerebrospinal fluid biomarkers). Standard 30-minute EEG may not be sufficiently sensitive to detect epileptiform discharges. In the present study, we aim to review different aspects of seizure in AD, including seizure prevalence, risk factors, underlying mechanisms, electroencephalographic findings, clinical presentations, impact of seizures on AD, and treatment options.

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CitationGPTRetr817

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Cracking novel shared targets between epilepsy and Alzheimer's disease: need of the hour. Abstract of the paper: Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures. The role of seizures in early stages of pathogenesis of AD is still an issue to be resolved. So, it is well timed to analyze the common pathways involved in pathophysiology of AD and epilepsy. The present review focuses on similar potential underlying mechanisms which may be related to the causes of seizures in epilepsy and cognitive impairment in AD. The proposed review will focus on many possible newer targets like abnormal expression of various enzymes like GSK-3β, PP2A, PKC, tau hyperphosphorylation, MMPs, caspases, neuroinflammation and oxidative stress associated with number of neurodegenerative diseases linked with epilepsy. The brief about the prospective line of treatment of both diseases will also be discussed in the present review.

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CitationGPTRetr818

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: Subclinical epileptiform activity during sleep in Alzheimer's disease and mild cognitive impairment. Abstract of the paper: OBJECTIVE Recent findings suggested that subclinical epileptiform activity is prevalent during sleep in a significant proportion of Alzheimer's Disease (AD) patients. THE AIMS OF OUR STUDY WERE (A) comparing the frequency of subclinical epileptiform activity during the sleep in a sample diagnosed with 'probable' AD and Mild Cognitive Impairment (MCI) due to AD, and in healthy subjects; (B) evaluating epileptiform EEG activity as a function of different sleep stages within a well-controlled polysomnographic setting. METHODS We prospectively enrolled 50 'probable' AD patients (73 ± 7.0 years) and 50 subjects with MCI due to AD (72 ± 6.7 years) without history of seizures, comparing them with 50 controls (69 ± 6.7 years). Patients underwent to a full-night video-PSG. RESULTS Subclinical epileptiform activity was detected in 6.38% of 'probable' AD patients, 11.63% of MCI due to AD subjects and 4.54% of controls (p = 0.43). The comparisons between the three groups for the frequency of epileptiform activity did not reach statistically significant differences neither for total sleep nor for any sleep period considered. CONCLUSIONS Our study shows that, when controlling for sleep stages and the influence of psychoactive drugs, AD patients and MCI due to AD subjects do not exhibit a higher frequency of epileptiform discharges during sleep compared to healthy subjects. SIGNIFICANCE Subclinical epileptiform activity during sleep does not discriminate 'probable' AD from MCI due to AD and healthy controls.

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CitationGPTRetr819

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: nonconvulsive seizures and subclinical electroencephalography eeg abnormalities are common and underrecognized in ad patients and may accelerate structural and cognitive disorders Title of the paper: A Longitudinal Study of Epileptic Seizures in Alzheimer's Disease. Abstract of the paper: The prevalence of epileptic seizures is increased in patients in the clinical stages of Alzheimer's disease (AD) when compared to age-matched cognitively normal populations. In previously reported work from the Presentation of Epileptic Seizures in Dementia (PrESIDe) study, we identified a clinical suspicion of epilepsy in between 12.75 and 28.43% of patients with AD recruited from a memory clinic. EEGs were not performed in this study. Patients with epilepsy performed similarly to patients without epilepsy on cognitive testing at the time of recruitment but were more impaired on two measures of everyday functioning [Cambridge Behavioral Inventory-Revised and Clinical Dementia Rating (CBI-R and CDR)]. On repeated testing in this 12-month follow-up study, patients in whom a suspicion of epilepsy was identified performed significantly worse on cognitive function testing (p = 0.028) in addition to maintaining a difference on the informant questionnaires (CBI-R p < 0.001, CDR p = 0.020). These findings suggest that seizures in this population could be a marker of a more rapid decline and worse prognosis.

False

CitationGPTRetr820

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-Derived Neurotrophic Factor: Three Ligands, Many Actions. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins which include nerve growth factor, neurotrophin 3, and neurotrophin 4. Studies over the last three decades have identified mature BDNF as a key regulator of neuronal differentiation, structure, and function; actions mediated by the TrkB receptor. More recently identified isoforms which are translated from the bdnf gene, including the uncleaved precursor, pro-BDNF, and the cleaved prodomain, have been found to elicit opposing functions in neurons through the activation of distinct receptors. This work emphasizes the critical roles for all three isoforms of BDNF in modulating neuronal activity that impact complex human behaviors including memory, anxiety, depression, and hyperphagia.

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CitationGPTRetr821

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: The role of brain derived neurotrophic factor in central nervous system. Abstract of the paper: Brain derived neurotrophic factor (BDNF) has multiple biological functions which are mediated by the activation of two receptors, tropomyosin receptor kinase B (TrkB) receptor and the p75 neurotrophin receptor, involving in physiological and pathological processes throughout life. The diverse presence and activity of BDNF indicate its potential role in the pathogenesis, progression and treatment of both neurological and psychiatric disorders. This review is to provide a comprehensive assessment of the current knowledge and future directions in BDNF-associated research in the central nervous system (CNS), with an emphasis on the physiological and pathological functions of BDNF as well as its potential treatment effects in CNS diseases, including depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cerebral ischemic stroke.

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CitationGPTRetr822

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Neurotrophin regulation of neural circuit development and function. Abstract of the paper: Brain-derived neurotrophic factor (BDNF)--a member of a small family of secreted proteins that includes nerve growth factor, neurotrophin 3 and neurotrophin 4--has emerged as a key regulator of neural circuit development and function. The expression, secretion and actions of BDNF are directly controlled by neural activity, and secreted BDNF is capable of mediating many activity-dependent processes in the mammalian brain, including neuronal differentiation and growth, synapse formation and plasticity, and higher cognitive functions. This Review summarizes some of the recent progress in understanding the cellular and molecular mechanisms underlying neurotrophin regulation of neural circuits. The focus of the article is on BDNF, as this is the most widely expressed and studied neurotrophin in the mammalian brain.

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CitationGPTRetr823

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor as a drug target for CNS disorders. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of trophic factors. BDNF is widely and abundantly expressed in the CNS and is available to some peripheral nervous system neurons that uptake the neurotrophin produced by peripheral tissues. BDNF promotes survival and differentiation of certain neuronal populations during development. In adulthood, BDNF can modulate neuronal synaptic strength and has been implicated in hippocampal mechanisms of learning and memory and spinal mechanisms for pain. Several CNS disorders are associated with a decrease in trophic support. As BDNF and its high affinity receptor are abundant throughout the whole CNS, and BDNF is a potent neuroprotective agent, this trophic factor is a good candidate for therapeutic treatment of some of CNS disorders. This review aims to correlate the features of some CNS disorders (Parkinson's disease, Alzheimer's disease, depression, epilepsy and chronic pain) to changes in BDNF expression in the brain. The cellular and molecular mechanism by which BDNF might be a therapeutic strategy are critically examined.

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CitationGPTRetr824

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a small dimeric protein, structurally related to nerve growth factor, which is abundantly and widely expressed in the adult mammalian brain. BDNF has been found to promote survival of all major neuronal types affected in Alzheimer's disease and Parkinson's disease, like hippocampal and neocortical neurons, cholinergic septal and basal forebrain neurons, and nigral dopaminergic neurons. In this article, we summarize recent work on the molecular and cellular biology of BDNF, including current ideas about its intracellular trafficking, regulated synthesis and release, and actions at the synaptic level, which have considerably expanded our conception of BDNF actions in the central nervous system. But our primary aim is to review the literature regarding BDNF distribution in the human brain, and the modifications of BDNF expression which occur in the brain of individuals with Alzheimer's disease and Parkinson's disease. Our knowledge concerning BDNF actions on the neuronal populations affected in these pathological states is also reviewed, with an aim at understanding its pathogenic and pathophysiological relevance.

True

CitationGPTRetr825

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Abstract of the paper: Brain Derived Neurotrophic Factor (BDNF) is a key molecule involved in plastic changes related to learning and memory. The expression of BDNF is highly regulated, and can lead to great variability in BDNF levels in healthy subjects. Changes in BDNF expression are associated with both normal and pathological aging and also psychiatric disease, in particular in structures important for memory processes such as the hippocampus and parahippocampal areas. Some interventions like exercise or antidepressant administration enhance the expression of BDNF in normal and pathological conditions. In this review, we will describe studies from rodents and humans to bring together research on how BDNF expression is regulated, how this expression changes in the pathological brain and also exciting work on how interventions known to enhance this neurotrophin could have clinical relevance. We propose that, although BDNF may not be a valid biomarker for neurodegenerative/neuropsychiatric diseases because of its disregulation common to many pathological conditions, it could be thought of as a marker that specifically relates to the occurrence and/or progression of the mnemonic symptoms that are common to many pathological conditions.

False

CitationGPTRetr826

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor and neuropsychiatric disorders. Abstract of the paper: Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in the central nervous system (CNS). It is essential for the development of the CNS and for neuronal plasticity. Because BDNF plays a crucial role in development and plasticity of the brain, it is widely implicated in psychiatric diseases. This review provides a summary of clinical and preclinical evidence for the involvement of this ubiquitous growth factor in major depressive disorder, schizophrenia, addiction, Rett syndrome, as well as other psychiatric and neurodevelopmental diseases. In addition, the review includes a discussion of the role of BDNF in the mechanism of action of pharmacological therapies currently used to treat these diseases, such antidepressants and antipsychotics. The review also covers a critique of experimental therapies such as BDNF mimetics and discusses the value of BDNF as a target for future drug development.

False

CitationGPTRetr827

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is one of the most widely distributed and extensively studied neurotrophins in the mammalian brain. Among its prominent functions, one can mention control of neuronal and glial development, neuroprotection, and modulation of both short- and long-lasting synaptic interactions, which are critical for cognition and memory. A wide spectrum of processes are controlled by BDNF, and the sometimes contradictory effects of its action can be explained based on its specific pattern of synthesis, comprising several intermediate biologically active isoforms that bind to different types of receptor, triggering several signaling pathways. The functions of BDNF must be discussed in close relation to the stage of brain development, the different cellular components of nervous tissue, as well as the molecular mechanisms of signal transduction activated under physiological and pathological conditions. In this review, we briefly summarize the current state of knowledge regarding the impact of BDNF on regulation of neurophysiological processes. The importance of BDNF for future studies aimed at disclosing mechanisms of activation of signaling pathways, neuro- and gliogenesis, as well as synaptic plasticity is highlighted.

False

CitationGPTRetr828

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have reported altered levels of BDNF in the circulation, i.e. serum or plasma, of patients with Alzheimer's disease (AD), and low BDNF levels in the CSF as predictor of future cognitive decline in healthy older subjects. Altered BDNF circulating levels have also been reported in other neurodegenerative and psychiatric disorders, hampering its use as a specific biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of neuropsychiatric disorders marked by neurodegenerative changes.

False

CitationGPTRetr829

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases. Abstract of the paper: It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and phospholipase C (PLC)-gamma pathways via activation of tropomyosin receptor kinase B (TrkB), a high affinity receptor for BDNF. Evidence has shown significant contributions of these signaling pathways in neurogenesis and synaptic plasticity in in vivo and in vitro experiments. Importantly, it has been demonstrated that dysfunction of the BDNF/TrkB system is involved in the onset of brain diseases, including neurodegenerative and psychiatric disorders. In this review, we discuss actions of BDNF and related signaling molecules on CNS neurons, and their contributions to the pathophysiology of brain diseases.

False

CitationGPTRetr830

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor, behavior, and new directions for the treatment of mental disorders. Abstract of the paper: Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this article is to point out evidence for the involvement of this molecule in the maintenance of normal cognitive and emotional functioning, and to outline recent developments using BDNF, or the regulation of endogenous BDNF expression, in the treatment of a variety of mental disorders. This article discusses the important role of BDNF in neuronal growth and survival, in modulating neurotransmission, in activity-directed synaptic remodeling, and in adult neurogenesis. We next outline evidence for the involvement of BDNF in complex behaviors such as learning, feeding, locomotion, responses to painful stimuli, and the management of severe stress. Finally, our review focuses on the involvement of BDNF in treatments for clinical depression and other chronic neurodegenerative processes. We discuss the way that current and future treatment development can be guided by our growing understanding of this molecule's actions in the brain and the ways the expression of BDNF can be regulated.

False

CitationGPTRetr831

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulation. Abstract of the paper: It is clear that brain-derived neurotrophic factor (BDNF) plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity. BDNF has emerged as one of the most important signaling molecules for the developing nervous system as well as the impaired nervous system, and multiple diseases, such as Alzheimer's, Parkinson's, Huntington's, epilepsy, Rett's syndrome, and psychiatric depression, are linked by their association with potential dysregulation of BDNF-driven signal transduction programs. These programs are responsible for controlling the amount of activated transcription factors, such as cAMP response element binding protein, that coordinate the expression of multiple brain proteins, like ion channels and early growth response factors, whose job is to maintain the balance of excitation and inhibition in the nervous system. In this review, we will explore the evidence for BDNF's role in gene regulation side by side with its potential role in the etiology of neurological diseases. It is hoped that by bringing the datasets together in these diverse fields we can help develop the foundation for future studies aimed at understanding basic principles of gene regulation in the nervous system and how they can be harnessed to develop new therapeutic opportunities.

False

CitationGPTRetr832

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: The Role of Brain-Derived Neurotrophic Factor Signaling in Central Nervous System Disease Pathogenesis. Abstract of the paper: Recent studies have found abnormal levels of brain-derived neurotrophic factor (BDNF) in a variety of central nervous system (CNS) diseases (e.g., stroke, depression, anxiety, Alzheimer's disease, and Parkinson's disease). This suggests that BDNF may be involved in the pathogenesis of these diseases. Moreover, regulating BDNF signaling may represent a potential treatment for such diseases. With reference to recent research papers in related fields, this article reviews the production and regulation of BDNF in CNS and the role of BDNF signaling disorders in these diseases. A brief introduction of the clinical application status of BDNF is also provided.

False

CitationGPTRetr833

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: BDNF signaling in context: From synaptic regulation to psychiatric disorders. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a neuropeptide that plays numerous important roles in synaptic development and plasticity. While its importance in fundamental physiology is well established, studies of BDNF often produce conflicting and unclear results, and the scope of existing research makes the prospect of setting future directions daunting. In this review, we examine the importance of spatial and temporal factors on BDNF activity, particularly in processes such as synaptogenesis, Hebbian plasticity, homeostatic plasticity, and the treatment of psychiatric disorders. Understanding the fundamental physiology of when, where, and how BDNF acts and new approaches to control BDNF signaling in time and space can contribute to improved therapeutics and patient outcomes.

False

CitationGPTRetr834

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-Derived Neurotrophic Factor in Alzheimer's Disease: Risk, Mechanisms, and Therapy. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) has a neurotrophic support on neuron of central nervous system (CNS) and is a key molecule in the maintenance of synaptic plasticity and memory storage in hippocampus. However, changes of BDNF level and expression have been reported in the CNS as well as blood of Alzheimer's disease (AD) patients in the last decade, which indicates a potential role of BDNF in the pathogenesis of AD. Therefore, this review aims to summarize the latest progress in the field of BDNF and its biological roles in AD pathogenesis. We will discuss the interaction between BDNF and amyloid beta (Aβ) peptide, the effect of BDNF on synaptic repair in AD, and the association between BDNF polymorphism and AD risk. The most important is, enlightening the detailed biological ability and complicated mechanisms of action of BDNF in the context of AD would provide a future BDNF-related remedy for AD, such as increment in the production or release of endogenous BDNF by some drugs or BDNF mimics.

False

CitationGPTRetr835

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function? Abstract of the paper: Low cerebral levels of brain-derived neurotrophic factor (BDNF), which plays a critical role in many brain functions, have been implicated in neurodegenerative, neurological and psychiatric diseases. Thus, increasing BDNF levels in the brain is considered an attractive possibility for the prevention/treatment of various brain diseases. To date, BDNF-based therapies have largely focused on neurons. However, given the cross-talk between endothelial cells and neurons and recent evidence that BDNF expressed by the cerebral endothelium largely accounts for BDNF levels present in the brain, it is likely that BDNF-based therapies would be most effective if they also targeted the cerebral endothelium. In this review, we summarize the available knowledge about the biology and actions of BDNF derived from endothelial cells of the cerebral microvasculature and we emphasize the remaining gaps and shortcomings.

False

CitationGPTRetr836

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Steroid hormones and BDNF. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.

False

CitationGPTRetr837

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor and its clinical implications. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

True

CitationGPTRetr838

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Brain-derived neurotrophic factor. Abstract of the paper: Since the purification of BDNF in 1982, a great deal of evidence has mounted for its central roles in brain development, physiology, and pathology. Aside from its importance in neural development and cell survival, BDNF appears essential to molecular mechanisms of synaptic plasticity. Basic activity-related changes in the central nervous system are thought to depend on BDNF modification of synaptic transmission, especially in the hippocampus and neocortex. Pathologic levels of BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy and chronic pain sensitization, whereas application of the trophic properties of BDNF may lead to novel therapeutic options in neurodegenerative diseases and perhaps even in neuropsychiatric disorders.

False

CitationGPTRetr839

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in the central nervous system cns bdnf is expressed by a variety of neuronal and glial cell types Title of the paper: Mechanisms That Modulate and Diversify BDNF Functions: Implications for Hippocampal Synaptic Plasticity. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has pleiotropic effects on neuronal morphology and synaptic plasticity that underlie hippocampal circuit development and cognition. Recent advances established that BDNF function is controlled and diversified by molecular and cellular mechanisms including trafficking and subcellular compartmentalization of different Bdnf mRNA species, pre- vs. postsynaptic release of BDNF, control of BDNF signaling by tropomyosin receptor kinase B (TrkB) receptor interactors and conversion of pro-BDNF to mature BDNF and BDNF-propeptide. Defects in these regulatory mechanisms affect dendritic spine formation and morphology of pyramidal neurons as well as synaptic integration of newborn granule cells (GCs) into preexisting circuits of mature hippocampus, compromising the cognitive function. Here, we review recent findings describing novel dynamic mechanisms that diversify and locally control the function of BDNF in hippocampal neurons.

False

CitationGPTRetr840

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Steroid hormones and BDNF. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.

False

CitationGPTRetr841

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Sex differences in brain-derived neurotrophic factor signaling: Functions and implications. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) regulates diverse processes such as neuronal survival, differentiation, and plasticity. Accumulating evidence suggests that molecular events that direct sexual differentiation of the brain interact with BDNF signaling pathways. This Mini-Review first examines potential hormonal and epigenetic mechanisms through which sex influences BDNF signaling. We then examine how sex-specific regulation of BDNF signaling supports the development and function of sexually dimorphic neural circuits that underlie male-specific genital reflexes in rats and song production in birds. Finally, we discuss the implications of sex differences in BDNF signaling for gender-biased presentation of neurological and psychiatric diseases such as Alzheimer's disease. Although this Mini-Review focuses on BDNF, we try to convey the general message that sex influences brain functions in complex ways and underscore the requirement for and challenge of expanding research on sex differences in neuroscience. © 2016 Wiley Periodicals, Inc.

False

CitationGPTRetr842

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have reported altered levels of BDNF in the circulation, i.e. serum or plasma, of patients with Alzheimer's disease (AD), and low BDNF levels in the CSF as predictor of future cognitive decline in healthy older subjects. Altered BDNF circulating levels have also been reported in other neurodegenerative and psychiatric disorders, hampering its use as a specific biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of neuropsychiatric disorders marked by neurodegenerative changes.

False

CitationGPTRetr843

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Exercise and estrogen: common pathways in Alzheimer's disease pathology. Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by progressive declines in cognitive function. Current epidemiological data indicate significant sex-linked disparities, where females have a higher risk of developing AD compared with male counterparts. This disparity necessitates further investigations to uncover the pathological and molecular factors influencing these sex differences. Although the underlying pathways behind this observed disparity remain elusive, recent research points to menopausal estrogen loss as a potential factor. Estrogen holds a significant role in amyloid precursor protein (APP) processing and overall neuronal health through the regulation of brain-derived neurotrophic factor (BDNF), a factor that is also reduced in postmenopausal women. BDNF is a known contributor to neuronal health and its reduced expression is typically linked to AD disorders. Exercise is known to increase BDNF and may provide an accessible activity for postmenopausal women to reduce their risk of AD. This review aims to discuss the relationship between estrogen, exercise, and BDNF in AD pathology.

False

CitationGPTRetr844

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Involvement of brain-derived neurotrophic factor in late-life depression. Abstract of the paper: Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hypothesis of depression. Late-life depression is associated with disturbances in structural and neural plasticity as well as impairments in cognitive behavior. Stress and aging also play a crucial role in late-life depression. Many recent studies have suggested that not only expression of BDNF is decreased in the serum/plasma of patients with late-life depression, but structural abnormalities in the brain of these patients may be associated with a polymorphism in the BDNF gene, and that there is a relationship between a BDNF polymorphism and antidepressant remission rates. This review provides a critical review of the involvement of BDNF in major depression, in general, and in late-life depression, in particular.

False

CitationGPTRetr845

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: The Role of Brain-Derived Neurotrophic Factor Signaling in Central Nervous System Disease Pathogenesis. Abstract of the paper: Recent studies have found abnormal levels of brain-derived neurotrophic factor (BDNF) in a variety of central nervous system (CNS) diseases (e.g., stroke, depression, anxiety, Alzheimer's disease, and Parkinson's disease). This suggests that BDNF may be involved in the pathogenesis of these diseases. Moreover, regulating BDNF signaling may represent a potential treatment for such diseases. With reference to recent research papers in related fields, this article reviews the production and regulation of BDNF in CNS and the role of BDNF signaling disorders in these diseases. A brief introduction of the clinical application status of BDNF is also provided.

False

CitationGPTRetr846

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Actions of Brain-Derived Neurotrophic Factor and Glucocorticoid Stress in Neurogenesis. Abstract of the paper: Altered neurogenesis is suggested to be involved in the onset of brain diseases, including mental disorders and neurodegenerative diseases. Neurotrophic factors are well known for their positive effects on the proliferation/differentiation of both embryonic and adult neural stem/progenitor cells (NSCs/NPCs). Especially, brain-derived neurotrophic factor (BDNF) has been extensively investigated because of its roles in the differentiation/maturation of NSCs/NPCs. On the other hand, recent evidence indicates a negative impact of the stress hormone glucocorticoids (GCs) on the cell fate of NSCs/NPCs, which is also related to the pathophysiology of brain diseases, such as depression and autism spectrum disorder. Furthermore, studies including ours have demonstrated functional interactions between neurotrophic factors and GCs in neural events, including neurogenesis. In this review, we show and discuss relationships among the behaviors of NSCs/NPCs, BDNF, and GCs.

False

CitationGPTRetr847

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: The Evidence for Altered BDNF Expression in the Brain of Rats Reared or Housed in Social Isolation: A Systematic Review. Abstract of the paper: There is evidence that development and maintenance of neural connections are disrupted in major mental disorders, which indicates that neurotrophic factors could play a critical role in their pathogenesis. Stress is a well-established risk factor for psychopathology and recent research suggests that disrupted signaling via brain-derived neurotrophic factor (BDNF) may be involved in mediating the negative effects of stress on the brain. Social isolation of rats elicits chronic stress and is widely used as an animal model of mental disorders such as schizophrenia and depression. We carried out a systematic search of published studies to review current evidence for an altered expression of BDNF in the brain of rats reared or housed in social isolation. Across all age groups (post-weaning, adolescent, adult), majority of the identified studies (16/21) reported a decreased expression of BDNF in the hippocampus. There are far less published data on BDNF expression in other brain regions. Data are also scarce to assess the behavioral changes as a function of BDNF expression, but the downregulation of BDNF seems to be associated with increased anxiety-like symptoms. The reviewed data generally support the putative involvement of BDNF in the pathogenesis of stress-related mental illness. However, the mechanisms linking chronic social isolation, BDNF expression and the elicited behavioral alterations are currently unknown.

False

CitationGPTRetr848

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Brain-Derived Neurotrophic Factor in Alzheimer's Disease: Risk, Mechanisms, and Therapy. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) has a neurotrophic support on neuron of central nervous system (CNS) and is a key molecule in the maintenance of synaptic plasticity and memory storage in hippocampus. However, changes of BDNF level and expression have been reported in the CNS as well as blood of Alzheimer's disease (AD) patients in the last decade, which indicates a potential role of BDNF in the pathogenesis of AD. Therefore, this review aims to summarize the latest progress in the field of BDNF and its biological roles in AD pathogenesis. We will discuss the interaction between BDNF and amyloid beta (Aβ) peptide, the effect of BDNF on synaptic repair in AD, and the association between BDNF polymorphism and AD risk. The most important is, enlightening the detailed biological ability and complicated mechanisms of action of BDNF in the context of AD would provide a future BDNF-related remedy for AD, such as increment in the production or release of endogenous BDNF by some drugs or BDNF mimics.

False

CitationGPTRetr849

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: BDNF mediates adaptive brain and body responses to energetic challenges. Abstract of the paper: Emerging findings suggest that brain-derived neurotrophic factor (BDNF) serves widespread roles in regulating energy homeostasis by controlling patterns of feeding and physical activity, and by modulating glucose metabolism in peripheral tissues. BDNF mediates the beneficial effects of energetic challenges such as vigorous exercise and fasting on cognition, mood, cardiovascular function, and on peripheral metabolism. By stimulating glucose transport and mitochondrial biogenesis BDNF bolsters cellular bioenergetics and protects neurons against injury and disease. By acting in the brain and periphery, BDNF increases insulin sensitivity and parasympathetic tone. Genetic factors, a 'couch potato' lifestyle, and chronic stress impair BDNF signaling, and this may contribute to the pathogenesis of metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes, and neurological disorders.

False

CitationGPTRetr850

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Estrogen-growth factor interactions and their contributions to neurological disorders. Abstract of the paper: Estrogen has diverse and powerful effects in the brain, including actions on neurons, glia, and the vasculature. It is not surprising, therefore, that there are many changes in the female brain as serum estradiol levels rise and fall during the normal ovarian cycle. At times of life when estradiol levels change dramatically, such as puberty, postpartum, or menopause, there also are dramatic changes in the central nervous system. Changes that occur because of fluctuations in serum estrogen levels are potentially relevant to neurological disorders because symptoms often vary with the time of the ovarian cycle. Moreover, neurological disorders (eg, seizures and migraine) often increase in frequency in women when estradiol levels change. In this review, the contribution of 2 growth factors targeted by estrogen, the neurotrophin brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), will be discussed. Estrogen-sensitive response elements are present on the genes for both BDNF and VEGF, and they are potent modulators of neuronal, glial, and vascular function, making them logical candidates to mediate the multitude of effects of estrogen. In addition, BDNF induces neuropeptide Y, which has diverse actions that are relevant to estrogen action and to the same neurological disorders.

False

CitationGPTRetr851

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: New insights into brain BDNF function in normal aging and Alzheimer disease. Abstract of the paper: The decline observed during aging involves multiple factors that influence several systems. It is the case for learning and memory processes which are severely reduced with aging. It is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging.

False

CitationGPTRetr852

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease. Abstract of the paper: Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer's disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.

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CitationGPTRetr853

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) is a small dimeric protein, structurally related to nerve growth factor, which is abundantly and widely expressed in the adult mammalian brain. BDNF has been found to promote survival of all major neuronal types affected in Alzheimer's disease and Parkinson's disease, like hippocampal and neocortical neurons, cholinergic septal and basal forebrain neurons, and nigral dopaminergic neurons. In this article, we summarize recent work on the molecular and cellular biology of BDNF, including current ideas about its intracellular trafficking, regulated synthesis and release, and actions at the synaptic level, which have considerably expanded our conception of BDNF actions in the central nervous system. But our primary aim is to review the literature regarding BDNF distribution in the human brain, and the modifications of BDNF expression which occur in the brain of individuals with Alzheimer's disease and Parkinson's disease. Our knowledge concerning BDNF actions on the neuronal populations affected in these pathological states is also reviewed, with an aim at understanding its pathogenic and pathophysiological relevance.

False

CitationGPTRetr854

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulation. Abstract of the paper: It is clear that brain-derived neurotrophic factor (BDNF) plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity. BDNF has emerged as one of the most important signaling molecules for the developing nervous system as well as the impaired nervous system, and multiple diseases, such as Alzheimer's, Parkinson's, Huntington's, epilepsy, Rett's syndrome, and psychiatric depression, are linked by their association with potential dysregulation of BDNF-driven signal transduction programs. These programs are responsible for controlling the amount of activated transcription factors, such as cAMP response element binding protein, that coordinate the expression of multiple brain proteins, like ion channels and early growth response factors, whose job is to maintain the balance of excitation and inhibition in the nervous system. In this review, we will explore the evidence for BDNF's role in gene regulation side by side with its potential role in the etiology of neurological diseases. It is hoped that by bringing the datasets together in these diverse fields we can help develop the foundation for future studies aimed at understanding basic principles of gene regulation in the nervous system and how they can be harnessed to develop new therapeutic opportunities.

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CitationGPTRetr855

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Abstract of the paper: Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Brain-derived neurotrophic factor (BDNF) is abundant in the brain and periphery, and is found in both human serum and plasma. Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood. These alterations of BDNF levels or neuronal plasticity in MDD patients before and after antidepressant treatment can be measured through the examination of serum or plasma BDNF concentrations. BDNF levels can therefore be useful markers for clinical response or improvement of depressive symptoms, but they are not diagnostic markers of major depression.

False

CitationGPTRetr856

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Abstract of the paper: Brain Derived Neurotrophic Factor (BDNF) is a key molecule involved in plastic changes related to learning and memory. The expression of BDNF is highly regulated, and can lead to great variability in BDNF levels in healthy subjects. Changes in BDNF expression are associated with both normal and pathological aging and also psychiatric disease, in particular in structures important for memory processes such as the hippocampus and parahippocampal areas. Some interventions like exercise or antidepressant administration enhance the expression of BDNF in normal and pathological conditions. In this review, we will describe studies from rodents and humans to bring together research on how BDNF expression is regulated, how this expression changes in the pathological brain and also exciting work on how interventions known to enhance this neurotrophin could have clinical relevance. We propose that, although BDNF may not be a valid biomarker for neurodegenerative/neuropsychiatric diseases because of its disregulation common to many pathological conditions, it could be thought of as a marker that specifically relates to the occurrence and/or progression of the mnemonic symptoms that are common to many pathological conditions.

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CitationGPTRetr857

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Brain-derived neurotrophic factor and its clinical implications. Abstract of the paper: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

True

CitationGPTRetr858

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: Brain-Derived Neurotrophic Factor and Diabetes. Abstract of the paper: Diabetes and its chronic complications still represent a great clinical problem, despite improvements made in the diagnosis and treatment of the disease. People with diabetes have a much higher risk of impaired brain function and psychiatric disorders. Neurotrophins are factors that protect neuronal tissue and improve the function of the central nervous system, and among them is brain-derived neurotrophic factor (BDNF). The level and function of BDNF in diabetes seems to be disturbed by and connected with the presence of insulin resistance. On the other hand, there is evidence for the highly beneficial impact of physical activity on brain function and BDNF level. However, it is not clear if this protective phenomenon works in the presence of diabetes. In this review, we summarize the current available research on this topic and find that the results of published studies are ambiguous.

True

CitationGPTRetr859

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: bdnf levels are known to fluctuate in response to factors such as age sex hormones lifestyle and stress however chronic alterations in its expression can be indicative of or potentially lead to chronic diseases such as ad Title of the paper: The expanding role of BDNF: a therapeutic target for Alzheimer's disease? Abstract of the paper: Finding an effective treatment for chronic neurodegenerative disorders still represents an unmet goal. There is considerable evidence that such disorders represent a combination of genetic determinants and failure of neuroprotective mechanisms sparking a wider degree of interest in shedding light on the cellular changes responsible for these devastating disorders. Because of their role in survival or differentiation of developing neurons, as well as the recent discovery of their importance in regulating synaptic plasticity during adulthood, neurotrophic factors have been suggested as essential contributors of the etiology of neurodegenerative disorders. Alzheimer's disease (AD) is a complex, chronic, devastating disease that affects a high percentage of the population over 65 years of age. This review will focus on different pharmacological interventions that are currently in use or drugs under development, narrowing the therapeutic agents to those that interfere with the expression of the trophic factor brain-derived neurotrophic factor (BDNF), a molecule playing a pivotal role in synaptic plasticity and cognition. From these findings, it appears clear that BDNF is implicated in the mechanism of action of drugs that improve cognitive deficits in animal models of AD and in AD patients.

False

CitationGPTRetr860

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer's disease mouse model. Abstract of the paper: Clinical trials with rosiglitazone, a potent agonist at peroxisome proliferator-activated receptor gamma (PPARgamma) suggest an improvement of cognitive function in Alzheimer's disease (AD) patients. The mechanisms mediating this potential beneficial effect remain to be fully elucidated. In mice overexpressing mutant human amyloid precursor protein (hAPP), a model of AD, we found that memory impairment in the object recognition test was prevented and also reversed by chronic rosiglitazone treatment. Given the possible involvement of glucocorticoid receptors (GR) in the actions of PPARgamma-ligands, we studied the effect of chronic rosiglitazone treatment on GR levels in the hippocampus of hAPP mice. An early down-regulation of GR, not related to elevated plasma corticosterone levels, was found in different hippocampal subfields of the transgenic mice and this decrease was prevented by rosiglitazone. In parallel with behavioural studies, rosiglitazone also normalized GR levels in older animals. This effect may contribute to explain the attenuation of memory decline by PPARgamma activation in an AD mouse model.

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CitationGPTRetr861

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Abstract of the paper: The thiazolidinediones, such as rosiglitazone, increase peripheral insulin sensitivity and their use is proposed for the treatment of Alzheimer's disease. However, the mechanisms underlying the potential beneficial effects of rosiglitazone in Alzheimer's disease remain unclear. In previous studies, we observed that Tg2576 Alzheimer mice develop peripheral insulin resistance with age and have much higher serum corticosterone levels than wild-type mice when fasted overnight. We further showed that both of these defects can be ameliorated by rosiglitazone administration. Here, we report that during behavioral testing which involves repetitive overnight fasting, Tg2576 mice administered rosiglitazone exhibited better spatial learning and memory abilities and had lower serum corticosterone levels than untreated Tg2576 mice. When untreated Tg2576 mice were administered metyrapone, a drug that blocks glucocorticoid production, their spatial learning and memory abilities and serum corticosterone levels were similar to those of rosiglitazone-treated mice. We further report here that rosiglitazone attenuated reductions in insulin-degrading enzyme (IDE) mRNA and activity, and reduced amyloid beta-peptide (Abeta)42 levels without affecting amyloid deposition, in the brains of Tg2576 mice. These results demonstrate that rosiglitazone attenuates learning and memory deficits in Tg2576 mice and suggest that the effects of the drug on learning and memory, brain IDE levels, and brain Abeta42 levels in the mice may be due to its glucocorticoid-lowering actions.

False

CitationGPTRetr862

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone rescues memory impairment in Alzheimer's transgenic mice: mechanisms involving a reduced amyloid and tau pathology. Abstract of the paper: Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARgamma) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARgamma, facilitated beta-amyloid peptide (Abeta) clearance. Rosiglitazone not only reduced Abeta burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients.

False

CitationGPTRetr863

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: PPARgamma agonists as therapeutics for the treatment of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid within the brain parenchyma and is accompanied by the impairment of neuronal metabolism and function, leading to extensive neuronal loss. The disease involves the perturbation of synaptic function, energy, and lipid metabolism. The development of amyloid plaques results in the induction of a microglial-mediated inflammatory response. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor whose biological actions are to regulate glucose and lipid metabolism and suppress inflammatory gene expression. Thus, agonists of this receptor represent an attractive therapeutic target for AD. There is now an extensive body of evidence that has demonstrated the efficacy of PPARgamma agonists in ameliorating disease-related pathology and improved learning and memory in animal models of AD. Recent clinical trials of the PPARgamma agonist rosiglitazone have shown significant improvement in memory and cognition in AD patients. Thus, PPARgamma represents an important new therapeutic target in treating AD.

False

CitationGPTRetr864

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Abstract of the paper: OBJECTIVE Insulin resistance (impaired insulin action) has been associated with Alzheimer disease (AD) and memory impairment, independent of AD. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists improve insulin sensitivity and regulate in-vitro processing of the amyloid precursor protein (APP). Authors evaluated the effects of the PPAR-gamma agonist rosiglitazone on cognition and plasma levels of the APP derivative beta-amyloid (Abeta) in humans. METHODS In a placebo-controlled, double-blind, parallel-group pilot study, 30 subjects with mild AD or amnestic mild cognitive impairment were randomized to a 6-month course of rosiglitazone (4 mg daily; N = 20) or placebo (N = 10). Primary endpoints were cognitive performance and plasma Abeta levels. RESULTS Relative to the placebo group, subjects receiving rosiglitazone exhibited better delayed recall (at Months 4 and 6) and selective attention (Month 6). At Month 6, plasma Abeta levels were unchanged from baseline for subjects receiving rosiglitazone but declined for subjects receiving placebo, consistent with recent reports that plasma Abeta42 decreases with progression of AD. CONCLUSIONS Findings provide preliminary support that rosiglitazone may offer a novel strategy for the treatment of cognitive decline associated with AD. Future confirmation in a larger study is needed to fully demonstrate rosiglitazone's therapeutic potential.

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CitationGPTRetr865

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: The impact of acute rosiglitazone on insulin pharmacokinetics at the blood-brain barrier. Abstract of the paper: INTRODUCTION CNS insulin levels are decreased and insulin receptor signalling is dampened in Alzheimer's disease (AD). Increasing CNS insulin levels through a variety of methods has been shown to improve memory. Indeed, medications routinely used to improve insulin resistance in type 2 diabetes are now being repurposed for memory enhancement. CNS insulin is primarily derived from the circulation, by an active transport system at the blood-brain barrier (BBB). The goal of this study was to determine whether rosiglitazone (RSG), a drug used to improve insulin sensitivity in type 2 diabetes, could enhance insulin transport at the BBB, as a potential therapeutic for improving memory. METHODS Using radioactively labelled insulin and the multiple-time regression analysis technique, we measured the rate of insulin BBB transport and level of vascular binding in mice pretreated with vehicle or 10 µg RSG in the presence or absence of an insulin receptor inhibitor. RESULTS Although we found acute RSG administration does not affect insulin transport at the BBB, it does restore BBB vascular binding of insulin in an insulin receptor-resistant state. CONCLUSIONS Acute RSG treatment does not alter insulin BBB transport in healthy mice but can restore insulin receptor binding at the BBB in an insulin-resistant state.

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CitationGPTRetr866

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPARγ more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPARγ agonists influence various pathologies in AD with emphasis on development of novel selective PPARγ modulators.

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CitationGPTRetr867

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone improves learning and memory ability in rats with type 2 diabetes through the insulin signaling pathway. Abstract of the paper: Diabetes mellitus (DM) is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that is referred to as diabetic encephalopathy. This study was performed to investigate the effect of rosiglitazone (RSG) on learning and memory in rats with DM and elucidate possible mechanisms underlying this condition. Thirty-two male Sprague-Dawley rats were randomly divided into 4 groups: control (C, n = 8), DM (n = 8), RSG-administered control (C + RSG, n = 8) and RSG-administered DM groups (DM + RSG, n = 8). At 8 weeks after drug administration, Morris water maze was used to perform a training and probe trial to detect spatial learning and memory abilities. Western blot and immunohistochemistry were also used to detect changes in proteins involved in the insulin signal transduction pathway, such as the insulin receptor, insulin receptor substrate-1, protein kinase B, phosphorylated cAMP response element-binding protein and B-cell lymphoma 2, in the hippocampus of the rats. This study found that RSG could normalize the impaired insulin signal transduction in type 2 DM. The authors showed that RSG modulated the central insulin signaling axis.

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CitationGPTRetr868

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Impact and Therapeutic Potential of PPARs in Alzheimer's Disease. Abstract of the paper: Peroxisome proliferator activated receptors (PPARs) are well studied for their role of peripheral metabolism, but they also may be involved in the pathogenesis of various disorders of the central nervous system (CNS) including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's and, Parkinson's disease. The observation that PPARs are able to suppress the inflammatory response in peripheral macrophages and in several models of human autoimmune diseases, lead to the idea that PPARs might be beneficial for CNS disorders possessing an inflammatory component. The neuroinflammatory response during the course of Alzheimer's disease (AD) is triggered by the deposition of the β-amyloid peptide in extracellular plaques and ongoing neurodegeneration. Non-steroidal anti-inflammatory drugs (NSAIDs) have been considered to delay the onset and reduce the risk to develop Alzheimer's disease, while they also directly activate PPARγ. This led to the hypothesis that NSAID protection in AD may be partly mediated by PPARγ. Several lines of evidence have supported this hypothesis, using AD related transgenic cellular and animal models. Stimulation of PPARγ by synthetic agonist (thiazolidinediones) inducing anti-inflammatory, anti-amyloidogenic and insulin sensitizing effects may account for the observed effects. Several clinical trials already revealed promising results using PPARγ agonists, therefore PPARγ represents an attractive therapeutic target for the treatment of AD.

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CitationGPTRetr869

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Enhancement of select cognitive domains with rosiglitazone implicates dorsal hippocampus circuitry sensitive to PPARγ agonism in an Alzheimer's mouse model. Abstract of the paper: INTRODUCTION Several clinical studies have tested the efficacy of insulin-sensitizing drugs for cognitive enhancement in Alzheimer's disease (AD) patients, as type 2 diabetes (T2D) is a well-recognized risk factor for AD. Pilot studies assessing FDA-approved diabetes drugs in subjects with early-stage disease have found cognitive benefit in subjects comorbid for insulin resistance. In AD mouse models with concomitant insulin resistance, we have shown that 4 weeks of RSG can reverse peripheral and central insulin resistance concomitant with rescue of hippocampus-dependent fear learning and memory and hippocampal circuitry deficits in 9-month-old (9MO) Tg2576 mice with no effect in wild-type (WT) mice. Bioinformatics analysis of genomic and proteomic data reveals an intimate link between PPARγ and MAPK/ERK signaling in the hippocampus. We then demonstrated a direct interaction between PPARγ and phospho-ERK in vitro and in vivo during memory consolidation. The translational value of this discovery is evidenced by the positive correlational relationship between human AD postmortem brain levels of pERK-PPARγ nuclear complexes with cognitive reserve. METHODS We tested whether insulin sensitizer therapy could rescue spatial navigation, context discrimination, and object recognition learning and memory in aged wild-type and Tg2576 mice in addition to hippocampus-dependent contextual fear learning and memory, as we have previously reported. RESULTS We found that rosiglitazone treatment improved cognitive domains that predominantly rely upon the dorsal hippocampus rather than those that additionally engage the ventral hippocampus. CONCLUSION These results suggest that insulin sensitizer therapy with rosiglitazone improved age- and AD-related learning and memory deficits in circuit selective ways.

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CitationGPTRetr870

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone reduces tau phosphorylation via JNK inhibition in the hippocampus of rats with type 2 diabetes and tau transfected SH-SY5Y cells. Abstract of the paper: Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. Rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, which is an anti-diabetic agent against type 2 diabetes, is currently in Phase III clinical trials in AD patients because rosiglitazone reduces β-amyloid (Aβ) pathology and inflammation. However, few studies have investigated whether rosiglitazone affects tau phosphorylation, another critical pathological feature of AD. Thus, we investigated it using OLETF type 2 diabetic rats and streptozotocin-injected type 1 diabetic mice. Interestingly, rosiglitazone reduced tau phosphorylation only in the hippocampus of OLETF type 2 diabetes rats, and not in that of STZ-injected type 1 diabetes mice. The activity of JNK was reduced in the hippocampus of rosiglitazone-treated OLETF rats, correlating with a reduction in tau phosphorylation, however, which was not correlated with GSK3β activity. In human tau-transfected SH-SY5Y neuronal cell line, reduction of tau phosphorylation was also associated with reduction of JNK activity, not of GSK3β activity. Hence, rosiglitazone could be used in reducing tau phosphorylation through JNK inactivation for therapeutic effects in type 2 diabetes related Alzheimer's disease.

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CitationGPTRetr871

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status. Abstract of the paper: Converging lines of evidence associate gluco-regulatory abnormalities and peroxisome-proliferator-activated receptor (PPAR) gamma function with increased risk for Alzheimer's disease (AD). In this study, we used the Tg2576 AD mouse model to test the hypothesis that cognitive improvement following 1 month of PPAR gamma agonism with rosiglitazone (RTZ) correlates with peripheral gluco-regulatory status. We assessed cognition and peripheral gluco-regulatory status of Tg2576 mice following 1 month treatment with RTZ initiated prior to, coincident with, or after, the onset of peripheral gluco-regulatory abnormalities (4, 8, and 12 months of age, respectively). Whereas 5 months old (MO) and 13 MO Tg2576 did not gain cognitive improvement after 1 month treatment with RTZ, 9 MO Tg2576 mice exhibited reversal of associative learning and memory deficits. Peripheral gluco-regulatory abnormalities were improved in 9 and 13 MO Tg2576 with RTZ treatment; RTZ treatment had no effect on the normal glucose status of 5 MO Tg2576 mice. These findings suggest that RTZ-mediated cognitive improvement does not correlate with peripheral gluco-regulatory abnormalities per se, but reflects the age-dependent mechanistic differences that underlie cognitive decline in this mouse model.

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CitationGPTRetr872

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via inhibition of inflammatory responses. Abstract of the paper: Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. In this study, Morris water maze test, ELISA and electrophysiological methods were used to examine the role and underling mechanisms of rosiglitazone on Aβ42 oligomer-induced memory impairments. We found that rosiglitazone attenuated Aβ42 oligomer-induced memory impairments in rats in a dose-dependent manner. The levels of inflammatory cytokines interleukin-1 beta (IL-1β) and interferon gamma (IFNγ) were significantly increased 7 days after injection of Aβ42 oligomers into the rat hippocampus. Inhibition of microglia activation prevented Aβ42 oligomer-induced increases in IL-1β and IFNγ levels. Rosiglitazone completely prevented the increase in the levels of IL-1β and IFNγ induced by Aβ42 oligomers. Treatment of hippocampal slices with the inflammatory cytokine IL-1β or IFNγ significantly inhibited the production of long-term potentiation (LTP) in the dentate gyrus. Rosiglitazone prevented the inhibitory effects of inflammatory cytokines on LTP. Thus, inhibition of inflammatory responses may be part of the mechanisms of action of rosiglitazone on preventing memory deficits induced by Aβ42 oligmers.

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CitationGPTRetr873

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone and pioglitazone for the treatment of Alzheimer's disease. Abstract of the paper: OBJECTIVE To review the literature on the efficacy and safety of rosiglitazone and pioglitazone for the treatment of Alzheimer's disease (AD). DATA SOURCES Literature was accessed through MEDLINE (1948-August 2011 week 2) and EMBASE (1980-2011 week 32) using the search terms rosiglita-zone, pioglitazone, and Alzheimer's disease. Results were limited to studies conducted in humans and published in English. STUDY SELECTION AND DATA EXTRACTION Clinical trials evaluating the efficacy and safety of rosiglitazone or pioglitazone in patients with AD were critically evaluated. DATA SYNTHESIS The mechanism for development of AD has been linked to both inflammation and decreased insulin sensitivity. Because of this, rosiglitazone and pioglitazone have been evaluated as potential treatments for AD because of their insulin-sensitizing and antiinflammatory effects. Five clinical trials were evaluated (3 assessing rosiglitazone, 2 assessing pioglitazone); 1 trial evaluating rosiglitazone demonstrated a beneficial effect on cognition in patients with probable AD. However, the largest randomized, double-blind, placebo-controlled trials conducted to date failed to demonstrate a difference between rosiglitazone and placebo when assessing primary endpoints. Two small trials evaluating pioglitazone produced conflicting results regarding efficacy in AD; numerous limitations make results difficult to interpret. The safety of these agents was also evaluated in these trials; edema was seen more commonly in patients receiving rosiglitazone or pioglitazone than in those receiving placebo; however, each drug was generally well tolerated. CONCLUSIONS Results from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended.

False

CitationGPTRetr874

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Abstract of the paper: INTRODUCTION Two phase 3 studies evaluated the efficacy and safety of rosiglitazone (RSG), a type 2 diabetes treatment, in an extended release (RSG XR) form as adjunctive therapy to ongoing acetylcholine esterase inhibitor (AChEI) treatment in AD (REFLECT-2, adjunctive to donepezil; REFLECT-3, to any AChEI). An open-label extension study (REFLECT-4) assessed RSG XR long-term safety. METHODS In these two double-blind, placebo-controlled studies, subjects with mild-to-moderate probable AD were randomized within 2 apolipoprotein E (APOE) allelic strata (APOE ε4-positive, APOE ε4-negative) to once daily placebo, 2 mg RSG XR, or 8 mg RSG XR for 48 weeks (REFLECT-2, N=1,496; REFLECT-3, N=1,485). Co-primary efficacy endpoints were change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) scores at week 48. Three populations were analyzed: APOE4-negative, all subjects except APOE ε4 homozygotes, and the full intent-to-treat population. RESULTS No statistically or clinically relevant differences between treatment groups were observed on the a priori primary endpoints in REFLECT-2 or REFLECT-3. Edema was the most frequent adverse event with RSG in each study (14% and 19%, respectively, at 8 mg RSG XR). CONCLUSIONS No evidence of statistically or clinically significant efficacy in cognition or global function was detected for 2 mg or 8 mg RSG XR as adjunctive therapy to ongoing AChEIs. There was no evidence of an interaction between treatment and APOE status. Safety and tolerability of RSG XR was consistent with the known profile of rosiglitazone.

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CitationGPTRetr875

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. Abstract of the paper: BACKGROUND/AIMS A phase II study of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer's disease (AD) detected a treatment benefit to cognition in apolipoprotein E(APOE)-ε4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate AD. An open-label extension study assessed the long-term safety and tolerability of 8 mg RSG XR. METHODS This double-blind, randomized, placebo-controlled study enrolled 693 subjects. Within 2 APOE allelic strata (ε4-positive, ε4-negative), subjects were randomized (2:2:2:1) to once-daily placebo, 2 mg RSG XR, 8 mg RSG XR or 10 mg donepezil (control). Coprimary endpoints were change from baseline to week 24 in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score, and week 24 Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+). RESULTS At week 24, no significant differences from placebo in change from baseline in coprimary endpoints were detected with either the RSG XR dose in APOE-ε4-negative subjects or overall. For donepezil, no significant treatment difference was detected in ADAS-Cog; however, a significant difference was detected (p = 0.009) on the CIBIC+. Peripheral edema was the most common adverse event for 8 mg RSG XR (15%) and placebo (5%), and nasopharyngitis for 2 mg RSG XR (7%). CONCLUSION No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-ε4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology.

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CitationGPTRetr876

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice. Abstract of the paper: Sporadic Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by progressive neurodegeneration. Decreased brain energy and glucose metabolism occurs before the appearance of AD symptoms and worsens while the disease progresses. Deregulated brain insulin signaling has also been found in AD recently. To restore brain insulin sensitivity and glucose metabolism, pioglitazone and rosiglitazone, two insulin sensitizers commonly used for treating type 2 diabetes, have been studied and shown to have some beneficial effects in AD mouse models. However, the molecular mechanisms of the beneficial effects remain elusive. In the present study, we treated the 3xTg-AD mice, a widely used mouse model of AD, with pioglitazone and rosiglitazone for 4 months and studied the effects of the treatments on cognitive performance and AD-related brain alterations. We found that the chronic treatment improved spatial learning, enhanced AKT signaling, and attenuated tau hyperphosphorylation and neuroinflammation. These findings shed new light on the possible mechanisms by which these two insulin sensitizers might be useful for treating AD and support further clinical trials evaluating the efficacy of these drugs.

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CitationGPTRetr877

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: PPARs in Alzheimer's Disease. Abstract of the paper: Peroxisome proliferator-activated receptors (PPARs) are well studied for their peripheral physiological and pathological impact, but they also play an important role for the pathogenesis of various disorders of the central nervous system (CNS) like multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's, and Parkinson's disease. The observation that PPARs are able to suppress the inflammatory response in peripheral macrophages and in several models of human autoimmune diseases lead to the idea that PPARs might be beneficial for CNS disorders possessing an inflammatory component. The neuroinflammatory response during the course of Alzheimer's disease (AD) is triggered by the neurodegeneration and the deposition of the beta-amyloid peptide in extracellular plaques. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been considered to delay the onset and reduce the risk to develop Alzheimer's disease, while they also directly activate PPARgamma. This led to the hypothesis that NSAID protection in AD may be partly mediated by PPARgamma. Several lines of evidence have supported this hypothesis, using AD-related transgenic cellular and animal models. Stimulation of PPARgamma receptors by synthetic agonist (thiazolidinediones) inducing anti-inflammatory, anti-amyloidogenic, and insulin sensitising effects may account for the observed effects. Several clinical trials already revealed promising results using PPAR agonists, therefore PPARs represent an attractive therapeutic target for the treatment of AD.

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CitationGPTRetr878

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Abstract of the paper: Mild-to-moderate AD patients were randomized to placebo or rosiglitazone (RSG) 2, 4 or 8 mg. Primary end points at Week 24 were mean change from baseline in AD Assessment Scale-Cognitive (ADAS-Cog) and Clinician's Interview-Based Impression of Change Plus Caregiver Input global scores in the intention-to-treat population (N=511), and results were also stratified by apolipoprotein E (APOE) genotype (n=323). No statistically significant differences on primary end points were detected between placebo and any RSG dose. There was a significant interaction between APOE epsilon4 allele status and ADAS-Cog (P=0.014). Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE epsilon4-negative patients on 8 mg RSG (P=0.024; not corrected for multiplicity). APOE epsilon4-positive patients did not show improvement and showed a decline at the lowest RSG dose (P=0.012; not corrected for multiplicity). Exploratory analyses suggested that APOE epsilon4 non-carriers exhibited cognitive and functional improvement in response to RSG, whereas APOE epsilon4 allele carriers showed no improvement and some decline was noted. These preliminary findings require confirmation in appropriate clinical studies.

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CitationGPTRetr879

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the effectiveness of rsg as a potential treatment for ad has mainly focused on its suppression of inflammatory genes transcription factors and molecular pathways Title of the paper: The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer's disease: therapeutic implications. Abstract of the paper: Alzheimer's disease is a complex neurodegenerative disorder, with aging, genetic and environmental factors contributing to its development and progression. The complexity of Alzheimer's disease presents substantial challenges for the development of new therapeutic agents. Alzheimer's disease is typified by pathological depositions of beta-amyloid peptides and neurofibrillary tangles within the diseased brain. It has also been demonstrated to be associated with a significant microglia-mediated inflammatory component, dysregulated lipid homeostasis and regional deficits in glucose metabolism within the brain. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a prototypical ligand-activated nuclear receptor that coordinates lipid, glucose and energy metabolism, and is found in elevated levels in the brains of individuals with Alzheimer's disease. A recently appreciated physiological function of this type of receptor is its ability to modulate inflammatory responses. In animal models of Alzheimer's disease, PPARgamma agonist treatment results in the reduction of amyloid plaque burden, reduced inflammation and reversal of disease-related behavioural impairment. In a recent phase II clinical trial, the use of the PPARgamma agonist rosiglitazone was associated with improved cognition and memory in patients with mild to moderate Alzheimer's disease. Thus, PPARgamma may act to modulate multiple pathophysiological mechanisms that contribute to Alzheimer's disease, and represents an attractive therapeutic target for the treatment of the disease.

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CitationGPTRetr880

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: The synaptic proteome in Alzheimer's disease. Abstract of the paper: BACKGROUND Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is recognized to be a primary pathological target for treatment. Synapse degeneration or dysfunction contributes to clinical signs of dementia through altered neuronal communication; the degree of synaptic loss correlates strongly with cognitive impairment. The molecular mechanisms underlying synaptic degeneration are still unclear, and identifying abnormally expressed synaptic proteins in AD brain will help to elucidate such mechanisms and to identify therapeutic targets that might slow AD progression. METHODS Synaptosomal fractions from human autopsy brain tissue from subjects with AD (n = 6) and without AD (n = 6) were compared using two-dimensional differential in-gel electrophoresis. AD pathology is region specific; human subjects can be highly variable in age, medication, and other factors. To counter these factors, two vulnerable areas (the hippocampus and the temporal cortex) were compared with two relatively spared areas (the motor and occipital cortices) within each group. Proteins exhibiting significant changes in expression were identified (≥20% change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption ionization time-of-flight or electrospray ionisation quadrupole-time of flight mass spectrometry. RESULTS Twenty-six different synaptic proteins exhibited more than twofold differences in expression between AD and normal subjects. These proteins are involved in regulating different cellular functions, including energy metabolism, signal transduction, vesicle transport, structure, and antioxidant activity. CONCLUSION Comparative proteome analysis uncovered markers of pathogenic mechanisms involved in synaptic dysfunction.

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CitationGPTRetr881

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: The role of synaptic proteins in the pathogenesis of disorders of the central nervous system. Abstract of the paper: Complex sets of nervous system functions are dependent on proper working of the synaptic apparatus, and these functions are regulated by diverse synaptic proteins that are distributed in various subcellular compartments of the synapse. The most extensively studied synaptic proteins are synaptophysin, the synapsins, growth associated protein 43 (GAP-43), SV-2, and p65. Moreover, synaptic terminals contain a great number of other proteins involved in calcium transport, neurotransmission, signaling, growth and plasticity. Probes against various synaptic proteins have recently been used to study synaptic alterations in human disease, as well as in experimental models of neurological disorders. Such probes are useful markers of synaptic function and synaptic population density in the nervous system. For the present, we will review the role of synaptic proteins in the following conditions: Alzheimer's disease (AD) and other disorders including ischemia, disorders where synapse-associated proteins are abnormally accumulated in the nerve terminals, synaptic proteins altered after denervation, and synaptic proteins as markers in neoplastic disorders. The study of the molecular alterations of the synapses and of plasticity might yield important clues as to the mechanisms of neurodegeneration in AD, and of the patterns of presynaptic and dendritic damage under diverse pathological conditions.

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CitationGPTRetr882

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Synaptic and neuritic alterations during the progression of Alzheimer's disease. Abstract of the paper: Extensive synaptic and neuritic alterations in the neocortex and limbic system are characteristically found in Alzheimer's disease (AD). However, it is not known how early in the development of the disease these alterations occur. For the present study, we compared the synaptic and neuritic alterations among cases classified clinically and neuropathologically as early, mild and advanced AD. In early AD there was a 20% loss of synaptophysin-immunoreactive presynaptic terminals in the outer molecular layer of the hippocampal dentate gyrus (but not in the neocortex and entorhinal cortex), accompanied by increased amyloid precursor protein (APP) and Alz50 immunoreactivity in hippocampal and entorhinal cortex pyramidal neurons. These results suggest that abnormal neuronal expression of APP and cytoskeletal proteins in early stages might be involved in the mechanisms of synaptic pathology in AD.

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CitationGPTRetr883

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Proteomic analysis of the brain in Alzheimer's disease: molecular phenotype of a complex disease process. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for about 50% of all dementias, yet its pathogenic mechanisms remain poorly understood. In order to provide a more complete picture of pathogenesis in AD, we analysed six human brain regions for alterations in their proteomes. Quantitative proteome analysis was used to compare signals corresponding to individual proteins between post mortem brain tissues from persons with AD, and those from age-matched nondemented control (NC) tissues. In severely injured brain regions, 76 proteins were differentially expressed in AD hippocampus compared with NC, 62 proteins were differentially expressed in temporal cortex, and 39 proteins were differentially expressed in entorhinal cortex. Significant differences were also present in relatively spared regions. Thus, 34 proteins were differentially expressed in AD cerebellum compared with NC, 125 proteins were differentially expressed in cingulate gyrus, and 75 proteins were differentially expressed in sensorimotor cortex. The identity of 37 of these proteins was determined, and the possible relevance of changes in key pathogenic pathways analysed. These studies provide a unique snapshot illustrating the complexity of interrelated disease mechanisms at work in a complex, multifactorial disease, and show that comparative proteome analysis is a method with the power to develop important new insights into pathogenic mechanisms in the dementias.

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CitationGPTRetr884

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Alzheimer's disease amyloid beta-protein and synaptic function. Abstract of the paper: Alzheimer's disease (AD) is characterized neuropathologically by the deposition of different forms of amyloid beta-protein (A beta) including variable amounts of soluble species that correlate with severity of dementia. The extent of synaptic loss in the brain provides the best morphological correlate of cognitive impairment in clinical AD. Animal research on the pathophysiology of AD has therefore focussed on how soluble A beta disrupts synaptic mechanisms in vulnerable brain regions such as the hippocampus. Synaptic plasticity in the form of persistent activity-dependent increases or decreases in synaptic strength provide a neurophysiological substrate for hippocampal-dependent learning and memory. Acute treatment with human-derived or chemically prepared soluble A beta that contains certain oligomeric assemblies, potently and selectively disrupts synaptic plasticity causing inhibition of long-term potentiation (LTP) and enhancement of long-term depression (LTD) of glutamatergic transmission. Over time these and related actions of A beta have been implicated in reducing synaptic integrity. This review addresses the involvement of neurotransmitter intercellular signaling in mediating or modulating the synaptic plasticity disrupting actions of soluble A beta, with particular emphasis on the different roles of glutamatergic and cholinergic mechanisms. There is growing evidence to support the view that NMDA and possibly nicotinic receptors are critically involved in mediating the disruptive effect of A beta and that targeting muscarinic receptors can indirectly modulate A beta's actions. Such studies should help inform ongoing and future clinical trials of drugs acting through the glutamatergic and cholinergic systems.

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CitationGPTRetr885

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Mechanisms of synaptic dysfunction in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is characterized by a progressive cognitive decline in which memory, initiation, learning and conceptualization are severely affected. The main histopathological alterations are the presence of amyloid beta/A4-containing plaques, tangles and amyloid angiopathy. It is believed that these brain alterations are associated with abnormal expression and/or processing of amyloid precursor protein (APP) and with abnormal assembly of cytoskeletal proteins. Recent quantitative studies with the electron microscope and with immunochemical/immunocytochemical assays, using molecular markers for synaptic proteins, have shown that synaptic loss in the cortex is the major correlate of the patterns of cognitive decline in AD. The synaptic loss in AD is accompanied by neuronal loss and aberrant sprouting, and studies in incipient AD cases have shown that this alteration occurs very early in the progression of the disease preceding tangle formation and neuronal loss. These results suggest that damage to the synaptic terminal plays a central role in the pathogenesis of AD. The mechanisms of synaptic pathology in AD are not yet clear, however, studies in transgenic animal models support the possibility that APP participates in synaptic stabilization and that abnormal metabolism of this molecule could lead to synaptic dysfunction which, in turn, results in neurodegeneration and dementia.

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CitationGPTRetr886

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Key Peptides and Proteins in Alzheimer's Disease. Abstract of the paper: Alzheimer's Disease (AD) is a form of progressive dementia involving cognitive impairment, loss of learning and memory. Different proteins (such as amyloid precursor protein (APP), β- amyloid (Aβ) and tau protein) play a key role in the initiation and progression of AD. We review the role of the most important proteins and peptides in AD pathogenesis. The structure, biosynthesis and physiological role of APP are shortly summarized. The details of trafficking and processing of APP to Aβ, the cytosolic intracellular Aβ domain (AICD) and small soluble proteins are shown, together with other amyloid-forming proteins such as tau and α-synuclein (α-syn). Hypothetic physiological functions of Aβ are summarized. The mechanism of conformational change, the formation and the role of neurotoxic amyloid oligomeric (oAβ) are shown. The fibril formation process and the co-existence of different steric structures (U-shaped and S-shaped) of Aβ monomers in mature fibrils are demonstrated. We summarize the known pathogenic and non-pathogenic mutations and show the toxic interactions of Aβ species after binding to cellular receptors. Tau phosphorylation, fibrillation, the molecular structure of tau filaments and their toxic effect on microtubules are shown. Development of Aβ and tau imaging in AD brain and CSF as well as blood biomarkers is shortly summarized. The most probable pathomechanisms of AD including the toxic effects of oAβ and tau; the three (biochemical, cellular and clinical) phases of AD are shown. Finally, the last section summarizes the present state of Aβ- and tau-directed therapies and future directions of AD research and drug development.

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CitationGPTRetr887

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis. Abstract of the paper: Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.

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CitationGPTRetr888

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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CitationGPTRetr889

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Amyloid precursor protein and neural development. Abstract of the paper: Interest in the amyloid precursor protein (APP) has increased in recent years due to its involvement in Alzheimer's disease. Since its molecular cloning, significant genetic and biochemical work has focused on the role of APP in the pathogenesis of this disease. Thus far, however, these studies have failed to deliver successful therapies. This suggests that understanding the basic biology of APP and its physiological role during development might be a crucial missing link for a better comprehension of Alzheimer's disease. Here, we present an overview of some of the key studies performed in various model organisms that have revealed roles for APP at different stages of neuronal development.

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CitationGPTRetr890

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Role of APP and Aβ in synaptic physiology. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of dementia in aging populations. Although amyloid plaques are the hallmark of AD, loss of synapses and synaptic dysfunction are closely associated with the duration and severity of cognitive impairment in AD patients. Amyloid precursor protein (APP) and its cleavage products including Aβ have been suggested as homeostatic regulators of synaptic activity. APP manipulation and Aβ application, in vitro and in vivo, affect synapse formation and synaptic transmission. Moreover, synaptic dysfunction and learning deficits precede Aβ plaque deposition, suggesting that synaptic alterations may underlie the initial development of the disease. Because of the pivotal role of APP and Aβ in AD pathogenesis, it is essential to understand how APP and Aβ modulate synaptic function. Here, we review the roles that APP and Aβ play at the synapses, with particular focus on recent findings for the importance of APP in synaptogenesis and synaptic function.

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CitationGPTRetr891

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Dysfunctional proteins in neuropsychiatric disorders: From neurodegeneration to autism spectrum disorders. Abstract of the paper: Despite fundamental differences in disease course and outcomes, neurodevelopmental (autism spectrum disorders - ASD) and neurodegenerative disorders (Alzheimer's disease - AD and Parkinson's disease - PD) present surprising, common traits in their molecular pathomechanisms. Uncontrolled oligomerization and aggregation of amyloid β (Aβ), microtubule-associated protein (MAP) tau, or α-synuclein (α-syn) contribute to synaptic impairment and the ensuing neuronal death in both AD and PD. Likewise, the pathogenesis of ASD may be attributed, at least in part, to synaptic dysfunction; attention has also been recently paid to irregularities in the metabolism and function of the Aβ precursor protein (APP), tau, or α-syn. Commonly affected elements include signaling pathways that regulate cellular metabolism and survival such as insulin/insulin-like growth factor (IGF) - PI3 kinase - Akt - mammalian target of rapamycin (mTOR), and a number of key synaptic proteins critically involved in neuronal communication. Understanding how these shared pathomechanism elements operate in different conditions may help identify common targets and therapeutic approaches.

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CitationGPTRetr892

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Synaptic proteins associated with cognitive performance and neuropathology in older humans revealed by multiplexed fractionated proteomics. Abstract of the paper: Alzheimer's disease (AD) is defined by the presence of abundant amyloid-β (Aβ) and tau neuropathology. While this neuropathology is necessary for AD diagnosis, it is not sufficient for causing cognitive impairment. Up to one third of community dwelling older adults harbor intermediate to high levels of AD neuropathology at death yet demonstrate no significant cognitive impairment. Conversely, there are individuals who exhibit dementia with no gross explanatory neuropathology. In prior studies, synapse loss correlated with cognitive impairment. To understand how synaptic composition changes in relation to neuropathology and cognition, multiplexed liquid chromatography mass-spectrometry was used to quantify enriched synaptic proteins from the parietal association cortex of 100 subjects with contrasting levels of AD pathology and cognitive performance. 123 unique proteins were significantly associated with diagnostic category. Functional analysis showed enrichment of serotonin release and oxidative phosphorylation categories in normal (cognitively unimpaired, low neuropathology) and "resilient" (unimpaired despite AD pathology) individuals. In contrast, frail individuals, (low pathology, impaired cognition) showed a metabolic shift towards glycolysis and increased presence of proteasome subunits.

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CitationGPTRetr893

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Pathology of presynaptic proteins in Alzheimer's disease: more than simple loss of terminals. Abstract of the paper: Synaptic pathology is receiving increased attention in the study of the pathophysiology of Alzheimer's disease. A review of the literature on synaptic pathology in Alzheimer's disease was undertaken, focused on five areas. First, concerning the molecular substrates of presynaptic terminal changes, not all proteins are equally affected. Second, all brain regions in Alzheimer's disease do not show equivalent presynaptic protein pathology, hippocampus tended to be most affected. Third, relationships between presynaptic and neurofibrillary tangle pathology tended to be stronger than relationships with plaques. Fourth, broadly speaking, more severe cognitive impairment was associated with more severe presynaptic pathology. Finally, the relationship of presynaptic pathology and stage of illness appeared complex, with some reports of increased presynaptic proteins in earlier phases of illness, but consistent decreases in later phases. Detailed studies of presynaptic pathology in transgenic mouse models related to Alzheimer's disease may provide important insights concerning these observations.

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CitationGPTRetr894

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: The inside-out amyloid hypothesis and synapse pathology in Alzheimer's disease. Abstract of the paper: Cumulative evidence in brains and cultured neurons of Alzheimer's disease (AD) transgenic mouse models, as well as in human postmortem AD brains, highlights that age-related increases in β-amyloid peptide (Aβ), particularly in endosomes near synapses, are involved in early synapse dysfunction. Our immunoelectron microscopy and high-resolution immunofluorescence microscopy studies show that this early subcellular Aβ accumulation leads to progressive Aβ aggregation and pathology, particularly within dystrophic neurites and synapses. These studies confirm that neuritic/synaptic Aβ accumulation is the nidus of plaque formation. Aβ-dependent synapse pathology in AD models is modulated by synaptic activity and is plaque independent. The amyloid precursor protein (APP) is normally transported down neurites and appears to be preferentially processed to Aβ at synapses. Synapses are sites of early Aβ accumulation and aberrant tau phosphorylation in AD, which alter the synaptic composition at early stages of the disease. Elucidating the normal role of APP, and potentially of Aβ, at synapses should provide important insights into the mechanism(s) of Aβ-induced synapse dysfunction in AD and how to therapeutically mitigate these dysfunctions.

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CitationGPTRetr895

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Neurochemical dissection of synaptic pathology in Alzheimer's disease. Abstract of the paper: Synaptic pathology has attained increasing attention as being central in the pathogenesis of Alzheimer's disease (AD). To address the question whether synaptic pathology in AD involves the whole synapse, or is limited to specific components thereof, we studied three different synaptic vesicle proteins (rab3a, synaptotagmin, synaptophysin) and also the presynaptic membrane protein GAP-43 and the postsynaptic protein neurogranin. The material included postmortem brain tissue (frontal cortex, hippocampus, and cerebellum) from 8 patients with early-onset AD (EAD), 11 patients with late-onset AD (LAD), 6 patients with vascular dementia (VAD), and 9 control subjects. A reduction of all synaptic proteins was found in AD, more pronounced in EAD than in LAD, in both the frontal cortex (EAD 30% to 70% vs. LAD 82% to 88% of control value) and hippocampus (EAD 22% to 82% vs. LAD 76% to 89% of control value), whereas only minor changes were found in VAD. The finding that all synaptic proteins were reduced in AD suggests a degeneration and loss of whole synaptic elements that are more pronounced in EAD than in LAD.

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CitationGPTRetr896

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Synaptic activity and Alzheimer's disease: a critical update. Abstract of the paper: Synapses have been known for many years to be the crucial target of pathology in different forms of dementia, in particular Alzheimer's disease (AD). Synapses and their appropriate activation or inhibition are fundamental for the proper brain function. Alterations in synaptic/neuronal activity and brain metabolism are considered among the earliest symptoms linked to the progression of AD, and lead to a central question in AD research: what is the role played by synaptic activity in AD pathogenesis? Intriguingly, in the last decade, important studies demonstrated that the state of activation of synapses affects the homeostasis of beta-amyloid (Aβ) and tau, both of which aggregate and accumulate during AD, and are involved in neuronal dysfunction. In this review we aim to summarize the up-to-date data linking synaptic/neuronal activity with Aβ and tau; moreover, we also intend to provide a critical overview on brain activity alterations in AD, and their role in the disease's pathophysiology.

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CitationGPTRetr897

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies. Abstract of the paper: Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly population, is characterized by progressive cognitive decline and pathological hallmarks of amyloid plaques and neurofibrillary tangles. However, its pathophysiological mechanisms are poorly understood, and diagnostic tools and interventions are limited. Here, we review recent research on the amyloid hypothesis and beta-amyloid-induced dysfunction of neuronal synapses through distinct cell surface receptors. We also review how tau protein leads to synaptotoxicity through pathological modification, localization, and propagation. Finally, we discuss experimental therapeutics for AD and propose potential applications of disease-modifying strategies targeting synaptic failure for improved treatment of AD.

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CitationGPTRetr898

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: A Closer Look into the Role of Protein Tau in the Identification of Promising Therapeutic Targets for Alzheimer's Disease. Abstract of the paper: One of the most commonly known chronic neurodegenerative disorders, Alzheimer's disease (AD), manifests the common type of dementia in 60⁻80% of cases. From a clinical standpoint, a patent cognitive decline and a severe change in personality, as caused by a loss of neurons, is usually evident in AD with about 50 million people affected in 2016. The disease progression in patients is distinguished by a gradual plummet in cognitive functions, eliciting symptoms such as memory loss, and eventually requiring full-time medical care. From a histopathological standpoint, the defining characteristics are intracellular aggregations of hyper-phosphorylated tau protein, known as neurofibrillary tangles (NFT), and depositions of amyloid β-peptides (Aβ) in the brain. The abnormal phosphorylation of tau protein is attributed to a wide gamut of neurological disorders known as tauopathies. In addition to the hyperphosphorylated tau lesions, neuroinflammatory processes could occur in a sustained manner through astro-glial activation, resulting in the disease progression. Recent findings have suggested a strong interplay between the mechanism of Tau phosphorylation, disruption of microtubules, and synaptic loss and pathology of AD. The mechanisms underlying these interactions along with their respective consequences in Tau pathology are still ill-defined. Thus, in this review: (1) we highlight the interplays existing between Tau pathology and AD; and (2) take a closer look into its role while identifying some promising therapeutic advances including state of the art imaging techniques.

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CitationGPTRetr899

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: while little is known about how most of these proteins are mechanistically involved in ad the role of some of these proteins in ad has been previously explored for example dnm1l synpo and ywhaz all appear to promote adassociated pathology Title of the paper: Amyloid Precursor Protein 𝛽CTF accumulates in synapses in sporadic and genetic forms of Alzheimer's disease. Abstract of the paper: AIMS Amyloid Precursor Protein (APP) 𝛽-C-terminal fragment (𝛽CTF) may have a neurotoxic role in Alzheimer´s disease (AD). 𝛽CTF accumulates in the brains of patients with sporadic (SAD) and genetic forms of Alzheimer's Disease (AD). Synapses degenerate early during the pathogenesis of AD. We studied whether the 𝛽CTF accumulates in synapses in SAD, autosomal dominant AD (ADAD) and Down syndrome (DS). METHODS We used Array tomography to determine APP at synapses in human AD tissue. We measured 𝛽CTF, A𝛽40, A𝛽42 and phosphorylated tau181 (p-tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls. RESULTS APP colocalized with pre- and post-synaptic markers in human AD brains. APP 𝛽CTF was enriched in AD synaptosomes. CONCLUSIONS We demonstrate that 𝛽CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for 𝛽CTF in synapse degeneration. Therapies aimed at mitigating 𝛽CTF accumulation could be potentially beneficial in AD.

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