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CitationGPTRetr11700

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Abstract of the paper: Amyloid imaging represents a major advance in neuroscience, enabling the detection and quantification of pathologic protein aggregations in the brain. In this review we survey current amyloid imaging techniques, focusing on positron emission tomography (PET) with (11)carbon-labelled Pittsburgh Compound-B ((11)C-PIB), the most extensively studied and best validated tracer. PIB binds specifically to fibrillar beta-amyloid (Abeta) deposits, and is a sensitive marker for Abeta pathology in cognitively normal older individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). PIB-PET provides us with a powerful tool to examine in vivo the relationship between amyloid deposition, clinical symptoms, and structural and functional brain changes in the continuum between normal aging and AD. Amyloid imaging studies support a model in which amyloid deposition is an early event on the path to dementia, beginning insidiously in cognitively normal individuals, and accompanied by subtle cognitive decline and functional and structural brain changes suggestive of incipient AD. As patients progress to dementia, clinical decline and neurodegeneration accelerate and proceed independently of amyloid accumulation. In the future, amyloid imaging is likely to supplement clinical evaluation in selecting patients for anti-amyloid therapies, while MRI and FDG-PET may be more appropriate markers of clinical progression.

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CitationGPTRetr11701

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Abstract of the paper: This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94-fold, p = 0.0001). Large increases also were observed in parietal (1.71-fold, p = 0.0002), temporal (1.52-fold, p = 0.002), and occipital (1.54-fold, p = 0.002) cortex and the striatum (1.76-fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 +/- 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F-fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.

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CitationGPTRetr11702

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: In vivo human amyloid imaging. Abstract of the paper: PET imaging agents such as Pittsburgh compound B (PiB) allow detection of fibrillar β-amyloid (Aβ) in vivo. In addition to quantification of Aβ deposition in mild cognitive impairment and Alzheimer's disease, PiB has also increased our understanding of Aβ deposition in older adults without cognitive impairment. In vivo Aβ deposition has been studied in relation to genotype, structural and functional brain changes, as well as alterations in biomarker levels. To date, several studies have reported changes in Aβ burden over time. This, together with investigation of the relationship between Aβ deposition and cognition, sets the stage for elucidation of the temporal sequence of the neurobiological events leading to cognitive decline. Furthermore, correlation of Aβ levels detected by PiB PET and those obtained from biopsy or postmortem specimens will allow more rigorous quantitative interpretation of PiB PET data in relation to neuropathological evaluation. Since the first human study in 2004, in vivo amyloid imaging has led to advances in our understanding of the role of Aβ deposition in human aging and cognitive decline, as well as provided new tools for patient selection and therapeutic monitoring in clinical trials.

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CitationGPTRetr11703

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications. Abstract of the paper: In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique.

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CitationGPTRetr11704

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Amyloid imaging in Alzheimer's disease and other dementias. Abstract of the paper: With the advent of new therapeutic strategies aimed at reducing β-amyloid (Aβ) burden in the brain to potentially prevent or delay functional and irreversible cognitive loss, there is increased interest in developing agents that allow assessment of Aβ burden in vivo. Molecular neuroimaging techniques such as positron emission tomography (PET), in conjunction with related biomarkers in plasma and cerebrospinal fluid, are proving valuable in the early and differential diagnosis of Alzheimer's disease (AD). (11)C-PiB PET has proven useful in the discrimination of dementias, showing significantly higher PiB retention in grey matter of AD patients when compared with healthy controls or patients with frontotemporal dementia. (11)C-PiB PET also appears to be more accurate than FDG for the diagnosis of AD. Despite apparently underestimating the Aβ burden in the brain, (11)C-PiB PET is an optimal method to differentiate healthy controls from AD, matching histopathological reports in aging and dementia and reflecting the true regional density of Aβ plaques in cortical areas. High striatal Aβ deposition seems to be typical for carriers of familial forms of AD, whilst ApoE ε4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non- ε4 carriers. Characterization of the binding properties of PiB has shown that despite binding to other misfolded proteins in vitro, PiB is extremely selective for Aβ at the concentrations achieved during a PET scan. Aβ burden as assessed by PET does not correlate with measures of cognition or cognitive decline in AD. Approximately 30% of apparently healthy older people, and 50-60% of people with mild cognitive impairment, present with cortical (11)C-PiB retention. In these groups, Aβ burden does correlate with episodic memory and rate of memory decline. These observations suggest that Aβ deposition is not part of normal ageing, supporting the hypothesis that Αβ deposition occurs well before the onset of symptoms and is likely to represent preclinical AD. Further longitudinal observations, coupled with different disease-specific tracers and biomarkers are required not only to confirm this hypothesis, but also to better elucidate the role of Αβ deposition in the course of Alzheimer's disease.

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CitationGPTRetr11705

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: PET imaging of brain amyloid in dementia: a review. Abstract of the paper: OBJECTIVE To review the rapidly expanding literature of amyloid PET imaging with particular attention to Pittsburgh compound-B (PIB) in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), fronto-temporal dementia (FTD), mild cognitive impairment (MCI) and cognitively normal volunteers. DESIGN Literature searches were performed using Medline up to February 2010. Individual articles were then examined for additional references not revealed by automated searches. This yielded 79 articles whose abstracts were read by the authors to select key papers. RESULTS Amyloid deposition assessed using PIB-PET is significantly elevated in AD and DLB compared to controls and those with FTD. In MCI, uptake is often intermediate between AD and normal ageing, and excessive amyloid burden in non-demented individuals with MCI are likely to represent high-risk cases. Amyloid deposition appears to be an early event, and as dementia progresses clinical decline seems to be more associated with neurodegeneration than amyloid burden. CONCLUSIONS PIB-PET imaging is a sensitive and specific marker for underlying Aβ amyloid deposition and represents an important investigative tool for examining the relationship between amyloid burden, clinical symptoms and structural and functional changes in dementia. Amyloid imaging may also be useful for selecting patients for anti-amyloid therapies. However, studies have identified PIB-positive cases in otherwise healthy older individuals (10-30%), limiting diagnostic specificity. Development of biomarkers for investigating other aspects of dementia pathology, i.e. soluble Aβ, tau, synuclein and brain inflammation would further inform our understanding and assist in studying disease-modifying and preventive treatments in dementia.

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CitationGPTRetr11706

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Imaging Alzheimer pathology in late-life depression with PET and Pittsburgh Compound-B. Abstract of the paper: There is increasing evidence for an empiric link between late-life depression and Alzheimer disease (AD). The neuropathology of AD, previously only confirmed at autopsy, may now be detectable in vivo using selective imaging ligands for beta-amyloid. Positron emission tomography (PET) with [11C] 6-OH-BTA-1 [Pittsburgh Compound-B (PiB)] has shown high tracer retention in cortical areas in patients with clinical diagnoses of probable AD and low retention in age-matched controls. We also previously reported variable PiB retention in patients with mild cognitive impairment (MCI). In this study, we used PiB-PET to evaluate whether amyloid is present in elders with treated major depression, many of whom have persistent cognitive impairment. We evaluated 9 subjects with remitted major depression [3M: 6F, mean (SD) age=71.8(5.7) y]. Seven of the 9 depressed subjects also met criteria for the diagnosis of MCI. PiB-PET data from healthy elders [n=8; mean (SD) age=71.5(3.0) y] were used for comparison. PET was acquired with arterial sampling and PiB retention was quantified using magnetic resonance imaging-guided cortical regions and graphical analysis of time-activity data; arterial line failure led to exclusion of 1 depressed subject. The data demonstrated variably elevated PiB retention. PiB retention in the 2 depressed subjects with normal cognitive ability was in the range of nondepressed cognitively normal subjects. PiB retention in 3 of the 6 depressed subjects with MCI fell in the range of subjects with AD. PiB retention in the remaining 3 depressed subjects with cooccurring MCI was variable and generally was intermediate to the other subjects. Our findings are consistent with and supportive of the hypothesis that depression may herald the development of AD in some individuals.

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CitationGPTRetr11707

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Comparison of MRI based and PET template based approaches in the quantitative analysis of amyloid imaging with PIB-PET. Abstract of the paper: RATIONALE [(11)C]Pittsburgh compound-B (PIB) has been the most widely used positron emission tomography (PET) imaging agent for brain amyloid. Several longitudinal studies evaluating the progression of Alzheimer's disease (AD), and numerous therapeutic intervention studies are underway using [(11)C]PIB PET as an AD biomarker. Quantitative analysis of [(11)C]PIB data requires the definition of regional volumes of interest. This investigation systematically compared two data analysis routes both using a probabilistic brain atlas with 11 bilateral regions. Route 1 used individually segmented structural magnetic resonance images (MRI) for each subject while Route 2 used a standardised [(11)C]PIB PET template. METHODS A total of 54 subjects, 20 with probable Alzheimer's disease (AD), 14 with amnestic Mild Cognitive Impairment (MCI) and 20 age-matched healthy controls, were scanned at two imaging centres either in London (UK) or in Turku (Finland). For all subjects structural volumetric MRI and [(11)C]PIB PET scans were acquired. Target-to-cerebellum ratios 40 min to 60 min post injection were used as outcome measures. Regional read outs for grey matter target regions were generated for both routes. Based on a composite neocortical, frontal, posterior cingulate, combined posterior cingulate and frontal cortical regions, scans were categorised into either 'PIB negative' (PIB-) or 'PIB positive' (PIB+) using previously reported cut-off target-to-cerebellar ratios of 1.41, 1.5 and 1.6, respectively. RESULTS Target-to-cerebellum ratios were greater when defined with a [(11)C]PIB PET template than with individual MRIs for all cortical regions regardless of diagnosis. This difference was highly significant for controls (p<0.001, paired samples t-test), less significant for MCIs and borderline for ADs. Assignment of subjects to raised or normal categories was the same with both routes with a 1.6 cut-off while with lower cut off using frontal cortex, and combined frontal cortex and posterior cingulate demonstrated similar results, while posterior cingulate alone demonstrated significantly higher proportion of controls as amyloid positive by Route 2. CONCLUSIONS Definition of cortical grey matter regions is more accurate when individually segmented MRIs (Route 1) were used rather than a population-based PET template (Route 2). The impact of this difference depends on the grey-to-white matter contrast in the PET images; specifically seen in healthy controls with high white matter and low grey matter uptake. When classifying AD, MCI and control subjects as normal or abnormal using large cortical regions; discordance was found between the MRI and template approach for those few subjects who presented with cortex-to-cerebellum ratios very close to the pre-assigned cut-off. However, posterior cingulate alone demonstrated significant discordance in healthy controls using template based approach. This study, therefore, demonstrates that the use of a [(11)C]PIB PET template (Route 2) is adequate for clinical diagnostic purposes, while MRI based analysis (Route 1) remains more appropriate for clinical research.

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CitationGPTRetr11708

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques. Abstract of the paper: The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The (11)C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in (11)C-PiB binding and the extent of agreement with neuropathological assessment have not been thoroughly investigated. Sojkova and colleagues [35] reported variable agreement between CERAD-based neuropathologic diagnosis of AD lesions and mean cortical PiB, suggesting the need for a more direct quantification of regional Aβ in relation to in vivo imaging. In the present study, we extend these findings by examining the correspondence among regional (11)C-PiB load, region-matched quantitative immunohistological assessments of Aβ and NFTs, and brain atrophy (MRI) in six older Baltimore Longitudinal Study of Aging participants who came to autopsy (imaging-autopsy interval range 0.2-2.4 years). The total number of Aβ plaques (6E10) and NFTs (PHF1) in paraffin sections from hippocampus, orbito-frontal cortex, anterior and posterior cingulate gyrus, precuneus and cerebellum was quantified using a technique guided by unbiased stereological principles. We report a general agreement between the regional measures of amyloid obtained via stereological assessment and imaging, with significant relationships evident for the anterior (r = 0.83; p = 0.04) and posterior (r = 0.94; p = 0.005) cingulate gyri, and the precuneus (r = 0.94; p = 0.005). No associations were observed between (11)C-PiB load and NFT count for any of the regions examined (p > 0.2 in all regions), or between regional Aβ or NFT counts and corresponding brain volumes. The strong associations of PiB retention with region-matched, quantitative analyses of Aβ in postmortem tissue offer support for the validity of (11)C-PiB-PET imaging as a method for evaluation of plaque burden in vivo.

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CitationGPTRetr11709

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Amyloid β accumulation assessed with ¹¹C-Pittsburgh compound B PET and postmortem neuropathology. Abstract of the paper: ¹¹C-Pittsburgh compound B (PiB) uptake in PET images is frequently used to analyze β amyloid (Aβ) deposition in living individuals, but its correlation with histologically determined Aβ has not been examined. Six individuals with dementia underwent PiB-PET imaging, and their brains were analyzed neuropathologically (mean interval between imaging and death: 816 days; PiB positive:negative, 3:3; male:female, 3:3; mean age: 84.0 years). PiB uptake (reported as standardized uptake value ratio [SUVR]) was analyzed in 11 cortical regions and 10 subcortical grey matter areas and compared with the Aβ load (% area [the percentage of total area positive for Aβ] and number of neuritic plaques) seen with immunohistochemical staining with an anti-Aβ 11-28 antibody. Two PiB-positive subjects had abundant neuritic plaques and were diagnosed with Alzheimer’s disease (AD). SUVR and % area were strongly correlated in the cortical regions of these subjects (subject 1: r = 0.65, p = 0.03; subject 2: r = 0.80, p = 0.003). The other PiBpositive subject (subject 3) showed focal PiB uptake. In subject 3 and the 3 PiB-negative subjects (subjects 4-6), there was no correlation between regional SUVR and % area or neuritic plaques. PiB uptake was not correlated with Aβ deposition in subcortical regions. High PiB positivity in the cerebral cortex suggests the presence of substantial Aβ deposition and neuritic plaques associated with the pathologic changes of AD. Our results suggest that high cortical SUVR is a reliable marker of AD. Subcortical PiB positivity must be interpreted more carefully.

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CitationGPTRetr11710

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Abstract of the paper: The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4'-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-epsilon4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Abeta) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Abeta-peptide related cerebral amyloidosis.

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CitationGPTRetr11711

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Abstract of the paper: OBJECTIVE Cerebrovascular deposition of beta-amyloid (cerebral amyloid angiopathy [CAA]) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated positron emission tomographic imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes. METHODS We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD). RESULTS All CAA and AD subjects were PiB-positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 +/- 0.06) relative to healthy control subjects (1.04 +/- 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 +/- 0.17; p = 0.002). The occipital-to-global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 +/- 0.07 vs 0.86 +/- 0.05; p = 0.003). INTERPRETATION We conclude that PiB-positron emission tomography can detect cerebrovascular beta-amyloid and may serve as a method for identifying the extent of CAA in living subjects.

True

CitationGPTRetr11712

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Molecular neuroimaging in Alzheimer's disease. Abstract of the paper: This article reviews current amyloid positron emission tomography (PET) imaging with particular attention to Pittsburgh compound-B (PiB), the most extensively investigated and validated tracer. PiB specifically binds to fibrillar β-amyloid deposits such as those found in the cerebral cortex and striatum. PiB-PET imaging is a sensitive and specific biologic marker for underlying amyloid deposition, which is an early event on the path to dementia. Amyloid imaging in healthy controls and patients with mild cognitive impairment may detect those at high risk of future Alzheimer's disease, identifying them as candidates for early preventive measures if and when they become available.

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CitationGPTRetr11713

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Using Pittsburgh Compound B for in vivo PET imaging of fibrillar amyloid-beta. Abstract of the paper: The development of Aβ-PET imaging agents has allowed for detection of fibrillar Aβ deposition in vivo and marks a major advancement in understanding the role of Aβ in Alzheimer's disease (AD). Imaging Aβ thus has many potential clinical benefits: early or perhaps preclinical detection of disease and accurately distinguishing AD from dementias of other non-Aβ causes in patients presenting with mild or atypical symptoms or confounding comorbidities (in which the distinction is difficult to make clinically). From a research perspective, imaging Aβ allows us to study relationships between amyloid pathology and changes in cognition, brain structure, and function across the continuum from normal aging to mild cognitive impairment (MCI) to AD; and to monitor the effectiveness of anti-Aβ drugs and relate them to neurodegeneration and clinical symptoms. Here, we will discuss the application of one of the most broadly studied and widely used Aβ imaging agents, Pittsburgh Compound-B (PiB).

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CitationGPTRetr11714

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. Abstract of the paper: PURPOSE Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. METHODS In this study 238 [(11)C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [(11)C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. RESULTS [(11)C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [(11)C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [(11)C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. CONCLUSION This study demonstrated the robustness of [(11)C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.

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CitationGPTRetr11715

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer's disease. Abstract of the paper: Recently developed positron emission tomography (PET) tracers, such as PIB and FDDNP, help to visualize amyloid plaques and neurofibrillary tangles in living subjects. FDDNP binds to both amyloid plaques and tangles, whereas PIB selectively labels amyloid plaques. Therefore, it will be interesting to see a direct comparison of the regional binding of the two radiotracers for plaques (PIB) and plaques and tangles (FDDNP) using multitracer PET imaging for both PIB and FDDNP in the same subjects with and without Alzheimer's disease. Here we report that multitracer PET images of PIB and FDDNP in the same Alzheimer subjects show negligible PIB but strong FDDNP binding in the medial temporal cortex (hippocampus, amygdala, and parahippocampal gyrus), whereas there are significant quantities of both PIB and FDDNP binding in neocortical areas. These results suggest that tangles rather than amyloid plaques are the dominant pathology in the medial temporal cortex of living Alzheimer patients. In nondemented elderly normal subjects, PIB binding shows a significant increase in the posterior cingulate cortex compared with other brain regions, whereas in the same normal subjects we found significant FDDNP binding in the medial temporal cortex. Interestingly, the medial temporal FDDNP uptake values in normal elderly subjects were inversely correlated with long delay recall scores in the California Verbal Learning Test, a measure of episodic memory performance. We conclude that multitracer PET imaging of amyloid plaques and tangles using FDDNP and PIB in both nondemented and demented subjects provides important insight into these complicated pathological processes in living subjects.

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CitationGPTRetr11716

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: PET imaging of amyloid deposition in patients with mild cognitive impairment. Abstract of the paper: It is of great clinical value to identify subjects at a high risk of developing AD. We previously found that the amyloid positron emission tomography (PET) tracer PIB showed a robust difference in retention in the brain between AD patients and healthy controls (HC). Twenty-one patients diagnosed with MCI (mean age 63.3+/-7.8 (S.D.) years) underwent PET studies with (11)C-PIB, and (18)F-fluoro-deoxy-glucose (FDG) to measure cerebral glucose metabolism, as well as assessment of cognitive function and CSF sampling. Reference group data from 27 AD patients and 6 healthy controls, respectively, were used for comparison. The mean cortical PIB retention for the MCI patients was intermediate compared to HC and AD. Seven MCI patients that later at clinical follow-up converted to AD (8.1+/-6.0 (S.D.) months) showed significant higher PIB retention compared to non-converting MCI patients and HC, respectively (ps<0.01). The PIB retention in MCI converters was comparable to AD patients (p>0.01). Correlations were observed in the MCI patients between PIB retention and CSF Abeta(1-42), total Tau and episodic memory, respectively.

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CitationGPTRetr11717

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Abstract of the paper: OBJECTIVE To compare carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) findings in patients with and without Alzheimer disease lesions in frontal cortical biopsy specimens. DESIGN Cross-sectional study of [11C]PiB PET findings in patients with or without beta-amyloid (Abeta) aggregates in frontal cortical biopsy specimens. SETTING Two university hospitals in Finland. Patients Ten patients who had undergone intraventricular pressure monitoring with a frontal cortical biopsy (evaluated for Abeta aggregates and hyperphosphorylated tau) for suspected normal-pressure hydrocephalus. INTERVENTIONS [11C]PiB PET and evaluation for cognitive impairment using a battery of neuropsychological tests. MAIN OUTCOME MEASURES Immunohistochemical evaluation for Abeta aggregates and hyperphosphorylated tau in the frontal cortical biopsy specimen and [11C]PiB PET. RESULTS In patients with Abeta aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [11C]PiB uptake (P < .05) in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal Abeta deposits. CONCLUSIONS Our study supports the use of noninvasive [11C]PiB PET in the assessment of Abeta deposition in the brain. Large prospective studies are required to verify whether [11C]PiB PET will be a diagnostic aid, particularly in early Alzheimer disease.

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CitationGPTRetr11718

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Development of positron emission tomography β-amyloid plaque imaging agents. Abstract of the paper: For 100 years, β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) have been recognized as the neuropathological hallmarks of Alzheimer's disease (AD), and their presence or absence could only be assessed postmortem using stains and dyes that identified these microscopic structures. Approximately 10 years ago, the first successful Aβ plaque-specific positron emission tomography (PET) imaging study was conducted in a living human subject clinically diagnosed with probable AD using the (11)C-labeled radiopharmaceutical Pittsburgh Compound B (PiB). Laboratory studies and preclinical evaluations to design PiB began a decade earlier than the first human PiB PET study and involved chemical modifications of different well-known dyes that bound specifically to the extended β-pleated sheets that comprise the fibrils of amyloid proteins such as Aβ plaques, NFTs, α-synuclein deposits, and prions. These preclinical studies were conducted in our laboratories at the University of Pittsburgh, starting with Congo red derivatives, followed by Chrysamine G derivatives, followed by X-series compounds, and finally with neutral derivatives of thioflavin-T. The in vitro and in vivo evaluations of the different derivatives as candidate PET radioligands for imaging Aβ plaques and neurofibrillary tangles in human brain are described in this review, along with the specific evaluation criteria by which the candidate radioligands were judged. Out of these studies came PiB, a PET radioligand that binds selectively and with high affinity to only fibrillar forms of Aβ. PiB has been used in many different human research protocols throughout the world and has demonstrated the usefulness of assessing the Aβ plaque status of subjects many years before the clinical diagnosis of probable AD. Recently, longer-lived (18)F-radiolabeled Aβ-selective radiopharmaceuticals have been developed. It is likely that the full clinical impact of these imaging agents will be realized by identifying presymptomatic subjects who would benefit from early drug treatments with future disease-modifying AD therapeutics.

False

CitationGPTRetr11719

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: second one of the most exciting developments in neuroimaging has been the ability to label in vivo central amyloid depositions using a carbon11labeled lipophilic derivative of thioflavint termed pittsburgh compound b or simply pib pib can detect amyloid pathology even among nondemented individuals and has been associated with aβ42 levels in cerebrospinal fluid more recently two reports demonstrated that pib also reliably labels vascular deposition of aβ and is able to discriminate patients with clinically diagnosed cerebral amyloid angiopathy from those with ad thus while the culmination of studies reviewed above suggest that wmh are purely ischemic resulting from systemic or variable hypoperfusion multimodal neuroimaging and pathological examination would suggest a more heterogeneous profile perhaps with an amyloidogenic source of wmh distributed in posterior cortex among individuals with and at risk for ad Title of the paper: Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia. Abstract of the paper: UNLABELLED (11)C-Pittsburgh compound-B ((11)C-PiB) is the benchmark radiotracer for imaging of β-amyloid (Aβ) plaque in Alzheimer disease (AD). (18)F-labeled Aβ tracers subsequently developed for clinical use show higher nonspecific white matter binding and, in some cases, lower cortical binding in AD that could lead to less accurate interpretation of scans. We compared the cortical and white matter binding of a new (18)F-labeled Aβ tracer, (18)F-AZD4694 (recently renamed NAV4694), with (11)C-PiB in the same subjects. METHODS Forty-five participants underwent PET imaging with (11)C-PiB and (18)F-AZD4694 (25 healthy elderly controls [HCs], 10 subjects with mild cognitive impairment, 7 subjects with probable AD, and 3 subjects with probable frontotemporal dementia). Images were coregistered so that region-of-interest placement was identical on both scans, and standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were calculated between 40 and 70 min after injection for both tracers. RESULTS (18)F-AZD4694 showed reversible binding kinetics similar to (11)C-PiB, reaching an apparent steady state at 50 min after injection. Both radiotracers showed a similar dynamic range of neocortical SUVR (1.1-3.3 and 1.0-3.2 SUVR for (11)C-PiB and (18)F-AZD4694, respectively) and identical low nonspecific white matter binding, with frontal cortex-to-white matter ratios of 0.7 ± 0.2 and 1.3 ± 0.2 for both radiotracers in HCs and AD subjects, respectively. There was an excellent linear correlation between (11)C-PiB and (18)F-AZD4694 neocortical SUVR (slope of 0.95, r = 0.99, P < 0.0001). CONCLUSION (18)F-AZD4694 displays imaging characteristics nearly identical to those of (11)C-PiB. The low white matter and high cortical binding in AD indicate that this tracer is well suited to both clinical and research use.

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CitationGPTRetr11720

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex differences in β-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure. Abstract of the paper: The risk of Alzheimer's disease (AD) is higher in women than in men, a sex difference that likely results from the effects of sex steroid hormones. To investigate this relationship, we first compared progression of β-amyloid (Aβ) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly greater Aβ burden and larger behavioral deficits than age-matched males. Next, we evaluated how the organizational effects of sex steroid hormones during postnatal development may affect adult vulnerability to Aβ pathology. We observed that male 3xTg-AD mice demasculinized during early development exhibit significantly increased Aβ accumulation in adulthood. In contrast, female mice defeminized during early development exhibit a more male-like pattern of Aβ pathology in adulthood. Taken together, these results demonstrate significant sex differences in pathology in 3xTg-AD mice and suggest that these differences may be mediated by organizational actions of sex steroid hormones during development.

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CitationGPTRetr11721

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research. Abstract of the paper: Female sex is a leading risk factor for developing Alzheimer's disease (AD). Sexual dimorphism in AD is gaining attention as clinical data show that women are not only more likely to develop AD but also to experience worse pathology and faster cognitive decline. Pre-clinical AD research in animal models often neglects to address sexual dimorphism in evaluation of behavioral or molecular characteristics and outcomes. This can compromise its translation to a clinical setting. The triple-transgenic AD mouse model (3xTg-AD) is a commonly used but unique AD model because it exhibits both amyloid and tau pathology, essential features of the human AD phenotype. Mounting evidence has revealed important sexually dimorphic characteristics of this animal model that have yet to be reviewed and thus, are often overlooked in studies using the 3xTg-AD model. In this review we conduct a thorough analysis of reports of sexual dimorphism in the 3xTg-AD model including findings of molecular, behavioral, and longevity-related sex differences in original research articles through August 2020. Importantly, we find results to be inconsistent, and that strain source and differing methodologies are major contributors to lack of consensus regarding traits of each sex. We first touch on the nature of sexual dimorphism in clinical AD, followed by a brief summary of sexual dimorphism in other major AD murine models before discussing the 3xTg-AD model in depth. We conclude by offering four suggestions to help unify pre-clinical mouse model AD research inspired by the NIH expectations for considering sex as a biological variable.

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CitationGPTRetr11722

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Abstract of the paper: Epidemiological studies indicate that women have a higher risk of Alzheimer's disease (AD) even after adjustment for age. Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models. In this study, we found that female 3xTg-AD transgenic mice expressing mutant APP, presenilin-1 and tau have significantly more aggressive Abeta pathology. We also found an increase in beta-secretase activity and a reduction of neprilysin in female mice compared to males; this suggests that a combination of increased Abeta production and decreased Abeta degradation may contribute to higher risk of AD in females. In contrast to significantly more aggressive Abeta pathology in females, gender did not affect the levels of phosphorylated tau in 3xTg-AD mice. These results point to the involvement of Abeta pathways in the higher risk of AD in women. In addition to comparison of pathology between genders at 9, 16 and 23 months of age, we examined the progression of Abeta pathology at additional age points; i.e., brain Abeta load, intraneuronal oligomeric Abeta distribution and plaque load, in male 3xTg-AD mice at 3, 6, 9, 12, 16, 20 and 23 months of age. These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research.

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CitationGPTRetr11723

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex Dimorphism Profile of Alzheimer's Disease-Type Pathologies in an APP/PS1 Mouse Model. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by parenchymal and vascular beta-amyloid (Aβ) burden, tau pathology, neuroinflammation, and loss of neurons and synapses. There is a clear sex difference in the prevalence of AD. However, sex differences in AD-type pathologies have not been systematically documented. Applying 12-month-old female and male APP/PS1 mice as a model, we investigated the sex dimorphism in these major pathological indices. Compared with male APP/PS1 mice, the females exhibited higher parenchymal Aβ burdens, with the sex difference in hippocampus being the most significant. Female APP/PS1 mice had more severe cerebral amyloid angiopathy and subsequent microhemorrhage. In addition, female APP/PS1 mice also showed higher levels of phosphorylated tau and proinflammatory cytokines, more severe astrocytosis and microgliosis, and greater neuronal and synaptic degenerations. The present study systematically described a sex dimorphism in AD-type pathologic indices, suggesting that gender should be taken into account in designing studies involving these pathological indices and when interpreting the relevant findings in those studies.

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CitationGPTRetr11724

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Cognitive decline in Tg2576 mice shows sex-specific differences and correlates with cerebral amyloid-beta. Abstract of the paper: Patients suffering from Alzheimer's disease show a sex-dependent decline of cognitive function. The aim of this investigation was to show these differences in an animal model for Alzheimer's disease and to determine whether this effect is correlated to amyloid-beta-induced pathophysiological changes. Therefore, we assessed cognitive performance with the modified hole-board test in female and male Tg2576 and wild type mice at the age of 6, 8, 10, 12, 14, and 16 months and correlated these findings to the total amount of soluble amyloid-beta and insoluble amyloid deposits in the brain. Tg2576 mice perform worse than wild types. Female Tg2576 mice develop an accentuated cognitive impairment (wrong choice total) beginning at the age of 12 months compared to their male littermates. Alterations in the mice's behaviour do not show interference with these deficits. Cognitive impairment is correlated to the amount of soluble amyloid-beta and insoluble amyloid deposits in the brain in a sex-dependent manner.

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CitationGPTRetr11725

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex Differences in Alzheimer's Disease: Where Do We Stand? Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative disorder that drastically compromises patients' and relatives' quality of life, besides being a significant economic burden to global public health. Its pathophysiology is not completely elucidated yet, hence, the current therapies are restricted to treating the symptoms. Over the years, several epidemiological studies have shown disproportionalities in AD when sex is considered, which has encouraged researchers to investigate the potentiality of sex as a risk factor. Studies in rodent models have been used to investigate mechanistic basis of sex differences in AD, as well as the development of possible new sex-specific therapeutic strategies. However, full knowledge on factors related to this sexual dimorphism remains to be unraveled. Some findings point to differences in genetic and developmental backgrounds either earlier in life or in the aging brain. Herein we summarize the multisystemic framework behind the sex differences in AD and discuss the possible mechanisms involved in these differences raised by the literature so far in an integrative perspective.

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CitationGPTRetr11726

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex difference in Alzheimer's disease: An updated, balanced and emerging perspective on differing vulnerabilities. Abstract of the paper: Sex biology influences Alzheimer's disease (AD). Sex differences exist in the epidemiologic, imaging, biomarker, and pathology studies of this uniquely human condition. The mandate to understand sex differences in major diseases like AD is important for many reasons. First, AD is the most common neurodegenerative condition and a devastating disease-experienced as an insidious and progressive erosion of memory, cognition, and other brain functions. Second, since true sex differences in AD exist, their precise understanding could reveal what protects one sex or makes the other vulnerable-and this knowledge could inform development of new therapeutic approaches to benefit both sexes. Third, AD develops in the aging brain in a milieu of decreased circulating gonadal hormones. Thus, how sex-specific depletion affects the brain along with how replacement of androgens in men and estrogens and progestins in women alters vulnerability to AD are relevant questions, with clinical implications in a future of personalized medicine. This review will highlight advances in sex differences in AD in human populations with a focused perspective on epidemiology, biomarkers, and clinical trials. A thorough and concise overview of sex differences reviewed here indicates varying vulnerabilities in men and women. This review examines several lines of recent and strong evidence that collectively indicate the following: (1) men die faster with AD, (2) more women live with AD, (3) both sexes show similar risk of developing AD until advanced ages when women show increased risk, (4) both sexes show largely similar AD biomarker burden with notable exceptions for higher tau levels in subgroups of women with high amyloid, (5) women show brain reserve and resilience to tau pathology, (6) both sexes are vulnerable to the genetic risk of carrying APOE4, with women showing higher risk, and (7) neither sex has shown clear benefit of hormone replacement for AD or dementia risk in randomized clinical trials to date.

False

CitationGPTRetr11727

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex steroid levels and AD-like pathology in 3xTgAD mice. Abstract of the paper: Decreases in testosterone and 17β-oestradiol (E(2)) are associated with an increased risk for Alzheimer's disease (AD), which has been attributed to an increase in β-amyloid and tau pathological lesions. Although recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD-like pathology, almost none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age-related changes in testosterone and E(2) concentrations, as well as androgen receptor (AR) and oestrogen receptor (ER) α and β expression, in brain regions displaying AD pathology in intact male and female 3xTgAD and nontransgenic (ntg) mice. We report for the first time that circulating and brain testosterone levels significantly increase in male 3xTgAD mice with age, but without changes in AR-immunoreactive (IR) cell number in the hippocampal CA1 or medial amygdala. The age-related increase in hippocampal testosterone levels correlated positively with increases in the conformational tau isoform, Alz50. These data suggest that the over-expression of human tau up-regulate the hypothalamic-pituitary-gonadal axis in these mice. Although circulating and brain E(2) levels remained stable with age in both male and female 3xTgAD and ntg mice, ER-IR cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Furthermore, E(2) levels were significantly higher in the hippocampus than in serum, suggesting local production of E(2). Although triple transgenic mice mimic AD-like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions.

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CitationGPTRetr11728

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Gender dependent APP processing in a transgenic mouse model of Alzheimer's disease. Abstract of the paper: Epidemiological studies have reported a higher prevalence and incidence of Alzheimer's disease (AD) in women. The biochemical basis for this gender-disparate susceptibility is unknown. A gender effect on AD-typical plaque pathology has been shown in APP transgenic mouse models of AD. Female mice elicit higher plaque load than male mice. In an effort to analyze gender-dependent APP processing during postnatal development, we examined APP transgenic mice at time points prior to plaque deposition. At 14 weeks of age there was a significant elevation of C99 and Abeta in female mice compared to males. Furthermore we observed a slight decrease of BACE-activity in male mice as well as higher cerebral manganese levels in females. Although the decline in estrogen levels due to menopause in female patients is still discussed to be a risk factor for AD our results implicates that additional factors like modified BACE-activity or metal levels may contribute to the higher prevalence and incidence of AD in females.

False

CitationGPTRetr11729

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex differences in Alzheimer's disease: Understanding the molecular impact. Abstract of the paper: Alzheimer's disease (AD) is a common neurodegenerative disorder that presents with cognitive impairment and behavioral disturbance. Approximately 5.5 million people in the United States live with AD, most of whom are over the age of 65 with two-thirds being woman. There have been major advancements over the last decade or so in the understanding of AD neuropathological changes and genetic involvement. However, studies of sex impact in AD have not been adequately integrated into the investigation of disease development and progression. It becomes indispensable to acknowledge in both basic science and clinical research studies the importance of understanding sex-specific differences in AD pathophysiology and pathogenesis, which could guide future effort in the discovery of novel targets for AD. Here, we review the latest and most relevant literature on this topic, highlighting the importance of understanding sex dimorphism from a molecular perspective and its association to clinical trial design and development in AD research field.

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CitationGPTRetr11730

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex and gender differences in Alzheimer's disease: recommendations for future research. Abstract of the paper: Alzheimer's disease (AD) disproportionately affects women in both prevalence and severity; however, the biologic mechanisms underlying these sex differences are not fully understood. Sex differences in the brain, such as in brain anatomy, age-related declines in brain volume, and brain glucose metabolism, have been documented and may be important in understanding AD etiology. The full impact of sex as a basic biologic variable on this neurodegenerative disease remains elusive. To address the evidence for sex differences in AD, the Society for Women's Health Research (SWHR) convened an interdisciplinary roundtable of experts from academia, clinical medicine, industry, and the government to discuss the state-of-the-science in sex and gender differences in AD. Roundtable participants were asked to address gaps in our knowledge and identify specific sex-based research questions for future areas of study.

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CitationGPTRetr11731

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Gender differences in the occurrence of Alzheimer's disease. Abstract of the paper: Prevalence studies on dementia generally show a higher risk in women than in men. American studies reported equal rates whereas European ones showed higher rates in women. Observational studies on hormone replacement therapy showed that treated women had a lower risk than untreated ones. Two large clinical trials in menopausal women did not find any protective effect of therapy with oestrogens or oestrogens plus progestinic hormones. However, as regards a potential protective role of female gonadal hormones on brain neurodegenerative diseases, this result cannot be considered conclusive since a large cohort study showed an increased risk of Alzheimer's disease (AD) in women who underwent early oophorectomy. A possible gender difference in the risk of AD is further supported by recent evidence suggesting that the brain's so-called cognitive reserve is reduced in women. The area of gender differences in AD and in neurodegenerative processes generally, although still largely unexplored, appears to offer great promise for the future development of better strategies of intervention for patients.

False

CitationGPTRetr11732

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex and the development of Alzheimer's disease. Abstract of the paper: Men and women exhibit differences in the development and progression of Alzheimer's disease (AD). The factors underlying the sex differences in AD are not well understood. This Review emphasizes the contributions of sex steroid hormones to the relationship between sex and AD. In women, events that decrease lifetime exposure to estrogens are generally associated with increased AD risk, whereas estrogen-based hormone therapy administered near the time of menopause may reduce AD risk. In men, estrogens do not exhibit age-related reduction and are not significantly associated with AD risk. Rather, normal age-related depletions of testosterone in plasma and brain predict enhanced vulnerability to AD. Both estrogens and androgens exert numerous protective actions in the adult brain that increase neural functioning and resilience as well as specifically attenuating multiple aspects of AD-related neuropathology. Aging diminishes the activational effects of sex hormones in sex-specific manners, which is hypothesized to contribute to the relationship between aging and AD. Sex steroid hormones may also drive sex differences in AD through their organizational effects during developmental sexual differentiation of the brain. Specifically, sex hormone actions during early development may confer inherent vulnerability of the female brain to development of AD in advanced age. The combined effects of organizational and activational effects of sex steroids yield distinct sex differences in AD pathogenesis, a significant variable that must be more rigorously considered in future research. © 2016 Wiley Periodicals, Inc.

False

CitationGPTRetr11733

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex Differences in the Genetic Architecture of Alzheimer's Disease. Abstract of the paper: PURPOSE OF REVIEW Summarize sex-specific contributors to the genetic architecture of Alzheimer's disease (AD). RECENT FINDINGS There are sex differences in the effects of Apolipoprotein E (APOE), genes along the APOE pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD. SUMMARY There is a lack of comprehensive assessments of sex differences in genome-wide analyses of AD and a need for more systematic reporting a sex-stratified genetic effects. The emerging emphasis on sex as a biological variable provides an opportunity for transdisciplinary collaborations aimed at addressing major analytical challenges that have hampered advancements in the field. Ultimately, sex-specific genetic association studies represent a logical first step towards precision medicine.

False

CitationGPTRetr11734

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Understanding the impact of sex and gender in Alzheimer's disease: A call to action. Abstract of the paper: INTRODUCTION Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches. METHODS The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD. RESULTS The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research. DISCUSSION The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.

False

CitationGPTRetr11735

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Abstract of the paper: We sought to determine if sex impacts the cognitive and neuropathological phenotype of the 3xTg-AD mice. We find that male and female 3xTg-AD mice show comparable impairments on Morris water maze (MWM) and inhibitory avoidance (IA) at 4 months. Shortly thereafter, however, the cognitive performance varies among the sexes, with females performing worse than males. These behavioral differences are not attributable to differences in Abeta or tau levels. The behavioral effect is transient as from 12 months onward, the disparity is no longer apparent. Because females perform worse than males on stressful tasks, we explored their corticosterone responses and find that young female 3xTg-AD mice show markedly heightened corticosterone response after 5 days of MWM training compared to age-matched male 3xTg-AD mice; this difference is no longer apparent in older mice. Thus, the enhanced corticosterone response of the young female mice likely underlies their poorer performance on stressful tasks.

False

CitationGPTRetr11736

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: [Sex differences in Alzheimer's disease]. Abstract of the paper: The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.

False

CitationGPTRetr11737

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition. Abstract of the paper: Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.

False

CitationGPTRetr11738

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Sex and gonadal hormones in mouse models of Alzheimer's disease: what is relevant to the human condition? Abstract of the paper: Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer's - and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer's disease (AD) with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases.

False

CitationGPTRetr11739

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: be it all as it may all these results are in agreement with our findings of a greater degree of aβ pathology in female versus male 3xtgad animals from 4 months of age this is also in agreement with recent results observed in anothere ad transgenic mouse model app23 as well as in line with clinical evidence of higher prevalence of ad in females Title of the paper: Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences. Abstract of the paper: With the aging of the population, the burden of Alzheimer's disease (AD) is rapidly expanding. More than 5 million people in the US alone are affected with AD and this number is expected to triple by 2050. While men may have a higher risk of mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, women are disproportionally affected with AD. One explanation is that men may die of competing causes of death earlier in life, so that only the most resilient men may survive to older ages. However, many other factors should also be considered to explain the sex differences. In this review, we discuss the differences observed in men versus women in the incidence and prevalence of MCI and AD, in the structure and function of the brain, and in the sex-specific and gender-specific risk and protective factors for AD. In medical research, sex refers to biological differences such as chromosomal differences (eg, XX versus XY chromosomes), gonadal differences, or hormonal differences. In contrast, gender refers to psychosocial and cultural differences between men and women (eg, access to education and occupation). Both factors play an important role in the development and progression of diseases, including AD. Understanding both sex- and gender-specific risk and protective factors for AD is critical for developing individualized interventions for the prevention and treatment of AD.

False

CitationGPTRetr11740

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration. Abstract of the paper: Autopsy studies have shown that about 55% of patients with frontotemporal lobar degeneration (FTLD) and 25% of patients with Alzheimer's disease (AD) harbour TDP-43 immunoreactive pathological changes in their brains. Using ELISA, we investigated whether we could detect the presence, or increased amounts, of TDP-43 in plasma of patients with FTLD and AD compared to normal control subjects. We detected elevated levels of TDP-43 protein in plasma of 46% patients with FTLD with clinical frontotemporal dementia (FTD) and 22% patients with AD, compared to 8% of control subjects. The proportions of patients with FTD and AD showing raised plasma TDP-43 levels correspond closely to those proportions known from autopsy studies to contain TDP-43 pathological changes in their brains. Raised TDP-43 plasma levels may thereby index TDP-43 pathology within the brain. Plasma TDP-43 levels may be a biomarker that can provide a laboratory test capable of identifying the presence of TDP-43 brain pathology in neurodegenerative disease during life. It may help to distinguish those cases of FTLD with ubiquitin/TDP-43 pathology in their brains from those with tauopathy. As a predictive test, plasma TDP-43 level may have great practical value in directing therapeutic strategies aimed at preventing or removing tau or TDP-43 pathological changes from the brain in FTLD and AD.

False

CitationGPTRetr11741

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Possible concurrence of TDP-43, tau and other proteins in amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Abstract of the paper: Transactivation response DNA-binding protein 43 kDa (TDP-43) has been regarded as a major component of ubiquitin-positive/tau-negative inclusions of motor neurons and the frontotemporal cortices in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Neurofibrillary tangles (NFT), an example of tau-positive inclusions, are biochemically and morphologically distinguished from TDP-43-positive inclusions, and are one of the pathological core features of Alzheimer disease (AD). Although ALS/FTLD and AD are distinct clinical entities, they can coexist in an individual patient. Whether concurrence of ALS/FTLD-TDP-43 and AD-tau is incidental is still controversial, because aging is a common risk factor for ALS/FTLD and AD development. Indeed, it remains unclear whether the pathogenesis of ALS/FTLD is a direct causal link to tau accumulation. Recent studies suggested that AD pathogenesis could cause the accumulation of TDP-43, while abnormal TDP-43 accumulation could also lead to abnormal tau expression. Overlapping presence of TDP-43 and tau, when observed in a brain during autopsy, should attract attention, and should initiate the search for the pathological substrate for this abnormal protein accumulation. In addition to tau, other proteins including α-synuclein and amyloid β should be also taken into account as candidates for an interaction with TDP-43. Awareness of a possible comorbidity between TDP-43, tau and other proteins in patients with ALS/FTLD will be useful for our understanding of the influence of these proteins on the disease development and its clinical manifestation.

False

CitationGPTRetr11742

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Biomarkers for diseases with TDP-43 pathology. Abstract of the paper: The discovery that aggregated transactive response DNA-binding protein 43 kDa (TDP-43) is the major component of pathological ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) caused seminal progress in the unveiling of the genetic bases and molecular characteristics of these now so-called TDP-43 proteinopathies. Substantial increase in the knowledge of clinic-pathological coherencies, especially for FTLD variants, could be made in the last decade, but also revealed a considerable complexity of TDP-43 pathology and often a poor correlation of clinical and molecular disease characteristics. To date, an underlying TDP-43 pathology can be predicted only for patients with mutations in the genes C9orf72 and GRN, but is dependent on neuropathological verification in patients without family history, which represent the majority of cases. As etiology-specific therapies for neurodegenerative proteinopathies are emerging, methods to forecast TDP-43 pathology at patients' lifetime are highly required. Here, we review the current status of research pursued to identify specific indicators to predict or exclude TDP-43 pathology in the ALS-FTLD spectrum disorders and findings on candidates for prognosis and monitoring of disease progression in TDP-43 proteinopathies with a focus on TDP-43 with its pathological forms, neurochemical and imaging biomarkers.

False

CitationGPTRetr11743

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis. Abstract of the paper: BACKGROUND Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are incurable, progressive and fatal neurodegenerative diseases with patients variably affected clinically by motor, behavior, and cognitive deficits. The accumulation of an RNA-binding protein, TDP-43, is the most significant pathological finding in approximately 95% of ALS cases and 50% of FTD cases, and discovery of this common pathological signature, together with an increasing understanding of the shared genetic basis of these disorders, has led to FTD and ALS being considered as part of a single disease continuum. Given the widespread aggregation and accumulation of TDP-43 in FTD-ALS spectrum disorder, TDP-43 may have potential as a biomarker in these diseases. METHODS We therefore conducted a systematic review and meta-analysis to evaluate the diagnostic utility of TDP-43 detected in the cerebrospinal fluid (CSF) of patients with FTD-ALS spectrum disorder. RESULTS From seven studies, our results demonstrate that patients with ALS have a statistically significantly higher level of TDP-43 in CSF (effect size 0.64, 95% CI: 0.1-1.19, p = 0.02). CONCLUSIONS These data suggest promise for the use of CSF TDP-43 as a biomarker for ALS.

False

CitationGPTRetr11744

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration. Abstract of the paper: Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases. Immunohistochemistry (IHC) for NeuN and other neuronal markers found numerous neurons lacking reactivity, suggesting NeuN may reflect neuron health rather than neuron loss in FTLD. We found three patterns of NeuN and pTDP-43 reactivity in our sample of cortical tissue representing three intracortical region-specific stages of FTLD-TDP progression: Group 1 showed low levels of pathological pTDP-43 and high levels NeuN, while Group 2 showed increased levels of pTDP-43, and Group 3 tissues were characterized by reduced staining for both pTDP-43 and NeuN. Comparison of non-C9orf72/GRN FTLD-TDP with cases linked to both GRN mutations and C9orf72 expansions showed a significantly increased frequency of Group 3 histopathology in the latter cases, suggesting more advanced cortical disease. Hence, we propose that IHC profiles of pTDP-43 and NeuN reflect the burden of pTDP-43 and its deleterious effects on neuron health.

False

CitationGPTRetr11745

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Reappraisal of TDP-43 pathology in FTLD-U subtypes. Abstract of the paper: Frontotemporal lobar degeneration with tau-negative, ubiquitin-immunoreactive (-ir) pathology (FTLD-U) is subclassified based on the type and cortical laminar distribution of neuronal inclusions. Following the discovery of the transactive response DNA-binding protein Mr 43 kD (TDP-43) as the ubiquitinated protein in most FTLD-U, the same pathological criteria have been used to classify FTLD cases based on TDP-43-ir changes. However, the fact that immunohistochemistry (IHC) for ubiquitin and TDP-43 each recognizes slightly different pathological changes in these cases means that the original FTLD-U subtype criteria may not be directly applicable for use with TDP-43 IHC. We formally re-evaluated the TDP-43-ir pathological features that characterize the different FTLD-U subtypes to see if the current classification could be refined. In our series of 78 cases, 81% were classified as one of the common FTLD-U subtypes (29% A, 35% B, 17% C). With TDP-43 IHC, each subtype demonstrated consistent intra-group pathological features and clear inter-group differences. The TDP-43-ir changes that characterized type A and C cases were similar to those seen with ubiquitin IHC; specifically, compact neuronal cytoplasmic inclusions (NCI), short thick dystrophic neurites (DN), and lentiform neuronal intranuclear inclusions concentrated in cortical layer II in type A cases, and a predominance of long thick DN in type C. However, type B cases showed significant differences with TDP-43 compared with ubiquitin IHC; with many diffuse granular NCI and wispy thread and dots-like profiles in all cortical layers. The remaining 15 cases (12 with C9orf72 mutations) showed changes that were consistent with combined type A and type B pathology. These findings suggest that the pathological criteria for subtyping FTLD cases based on TDP-43 IHC might benefit from some refinement that recognizes differences in the morphologies of NCI and neurites. Furthermore, there is a significant subset of cases (most with the C9orf72 mutation) with the pathological features of multiple FTLD-TDP subtypes for which appropriate classification is difficult.

False

CitationGPTRetr11746

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43 in aging and Alzheimer's disease - a review. Abstract of the paper: Transactive response DNA-binding protein of 43 kDa (TDP-43), an RNA and DNA binding protein involved in transcriptional repression, RNA splicing and RNA metabolism during the stress response, is the major component of neuronal inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions, now referred to as FTLD-TDP. While initially thought to be relatively specific to ALS and FTLD-TDP, TDP-43 pathology has now been detected in a number of other neurodegenerative diseases, many associated with tau pathology, including Guam Parkinson dementia complex and Alzheimer's disease (AD). TDP-43 pathology is detected in 25% to 50% of AD cases, especially those with more severe clinical phenotype and greater Alzheimer type pathology, as well as AD cases with hippocampal sclerosis (HS). HS is characterized by selective neuronal loss affecting CA1 sector of the hippocampus, and most cases of HS, with or without AD, have TDP-43 pathology. Whether TDP-43 pathology is merely an incidental finding in AD or actually contributing to the more severe clinical phenotype remains unresolved. Presence of TDP-43 in normal elderly, who are at increased risk for AD, would strengthen the argument that it is not merely a secondary or incidental finding in end stage AD. Limited studies suggest that TDP-43 pathology is infrequent in neurologically normal elderly (3% or less). We provide an overview of what is known about TDP-43 in AD, normal aging and in other disorders and suggest that TDP-43 proteinopathies be considered in two classes - primary and secondary.

False

CitationGPTRetr11747

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Abstract of the paper: Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic lateral sclerosis (ALS). Using biochemical and immunohistochemical analyses, we have identified a TAR DNA-binding protein of 43 kDa (TDP-43), a nuclear factor that functions in regulating transcription and alternative splicing, as a component of these structures in FTLD. Furthermore, skein-like inclusions, neuronal intranuclear inclusions, and glial inclusions in the spinal cord of ALS patients are also positive for TDP-43. Dephosphorylation treatment of the sarkosyl insoluble fraction has shown that abnormal phosphorylation takes place in accumulated TDP-43. The common occurrence of intracellular accumulations of TDP-43 supports the hypothesis that these disorders represent a clinicopathological entity of a single disease, and suggests that they can be newly classified as a proteinopathy of TDP-43.

False

CitationGPTRetr11748

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies. Abstract of the paper: Pathologic TAR-DNA-binding protein 43 (TDP-43) is a disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. We studied the presence, frequency, and distribution of TDP-43 pathology by immunohistochemistry and biochemistry in a series of clinically well-characterized tauopathy patient brains, including 182 Alzheimer disease (AD), 39 corticobasal degeneration, 77 progressive supranuclear palsy, and 12 Pick disease cases and investigated the clinical impact of concomitant TDP-43 pathology in these cases. TAR-DNA-binding protein 43 pathology was found in 25.8% of AD cases. It was restricted to the dentate gyrus and entorhinal cortex in approximately 75% of cases; approximately 25% showed more widespread TDP-43 pathology in frontal and temporal cortices, resembling the FTLD-U subtype associated with progranulin mutations. TAR-DNA-binding protein 43 pathology in AD was associated with significantly longer disease duration, but there was no association with the clinical presentation (148 cases diagnosed as AD and 34 cases diagnosed as frontotemporal lobar degeneration). Progressive supranuclear palsy and Pick disease cases showed no TDP-43 inclusions and no biochemical alterations of TDP-43. There was, however, a unique, predominantly glial TDP-43 pathology with staining of astrocytic plaque-like structures and coiled bodies in 15.4% of corticobasal degeneration cases; this was associated with biochemical TDP-43 changes similar to those in FTLD-U. These findings provide further insight into the burden and clinical significance of TDP-43 pathology in disorders other than FTLD-U and amyotrophic lateral sclerosis.

False

CitationGPTRetr11749

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Abstract of the paper: OBJECTIVE This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U. METHODS Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry. RESULTS TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity. INTERPRETATION These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of alpha-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.

True

CitationGPTRetr11750

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Phosphorylated TDP-43 in Alzheimer's disease and dementia with Lewy bodies. Abstract of the paper: Phosphorylated and proteolytically cleaved TDP-43 is a major component of the ubiquitin-positive inclusions in the most common pathological subtype of frontotemporal lobar degeneration (FTLD-U). Intracellular accumulation of TDP-43 is observed in a subpopulation of patients with other dementia disorders, including Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). However, the pathological significance of TDP-43 pathology in these disorders is unknown, since biochemical features of the TDP-43 accumulated in AD and DLB brains, especially its phosphorylation sites and pattern of fragmentation, are still unclear. To address these issues, we performed immunohistochemical and biochemical analyses of AD and DLB cases, using phosphorylation-dependent anti-TDP-43 antibodies. We found a higher frequency of pathological TDP-43 in AD (36-56%) and in DLB (53-60%) than previously reported. Of the TDP-43-positive cases, about 20-30% showed neocortical TDP-43 pathology resembling the FTLD-U subtype associated with progranulin gene (PGRN) mutations. Immunoblot analyses of the sarkosyl-insoluble fraction from cases with neocortical TDP-43 pathology showed intense staining of several low-molecular-weight bands, corresponding to C-terminal fragments of TDP-43. Interestingly, the band pattern of these C-terminal fragments in AD and DLB also corresponds to that previously observed in the FTLD-U subtype associated with PGRN mutations. These results suggest that the morphological and biochemical features of TDP-43 pathology are common between AD or DLB and a specific subtype of FTLD-U. There may be genetic factors, such as mutations or genetic variants of PGRN underlying the co-occurrence of abnormal deposition of TDP-43, tau and alpha-synuclein.

False

CitationGPTRetr11751

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Abstract of the paper: Pathological TDP-43 is the major disease protein in frontotemporal lobar degeneration characterized by ubiquitin inclusions (FTLD-U) with/without motor neuron disease (MND) and in amyotrophic lateral sclerosis (ALS). As Guamanian parkinsonism-dementia complex (PDC) or Guamanian ALS (G-PDC or G-ALS) of the Chamorro population may present clinically similar to FTLD-U and ALS, TDP-43 pathology may be present in the G-PDC and G-ALS. Thus, we examined cortical or spinal cord samples from 54 Guamanian subjects for evidence of TDP-43 pathology. In addition to cortical neurofibrillary and glial tau pathology, G-PDC was associated with cortical TDP-43 positive dystrophic neurites and neuronal and glial inclusions in gray and/or white matter. Biochemical analyses showed the presence of FTLD-U-like insoluble TDP-43 in G-PDC, but not in Guam controls (G-C). Spinal cord pathology of G-PDC or G-ALS was characterized by tau positive tangles as well as TDP-43 positive inclusions in lower motor neurons and glial cells. G-C had variable tau and negligible TDP-43 pathology. These results indicate that G-PDC and G-ALS are associated with pathological TDP-43 similar to FTLD-U with/without MND as well as ALS, and that neocortical or hippocampal TDP-43 pathology distinguishes controls from disease subjects better than tau pathology. Finally, we conclude that the spectrum of TDP-43 proteinopathies should be expanded to include neurodegenerative cognitive and motor diseases, affecting the Chamorro population of Guam.

False

CitationGPTRetr11752

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: The Role of TDP-43 in Alzheimer's Disease. Abstract of the paper: The transactive response DNA binding protein (TDP-43) has long been characterized as a main hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U, also known as FTLD-TDP). Several studies have indicated TDP-43 deposits in Alzheimer's disease (AD) brains and have robust connection with AD clinical phenotype. FTLD-U, which was symptomatically connected with AD, may be predictable for the comprehension of the role TDP-43 in AD. TDP-43 may contribute to AD through both β-amyloid (Aβ)-dependent and Aβ-independent pathways. In this article, we summarize the latest studies concerning the role of TDP-43 in AD and explore TDP-43 modulation as a potential therapeutic strategy for AD. However, to date, little of pieces of the research on TDP-43 have been performed to investigate the role in AD; more investigations need to be confirmed in the future.

False

CitationGPTRetr11753

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: β-amyloid triggers ALS-associated TDP-43 pathology in AD models. Abstract of the paper: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with loss of motor neurons in the brain and spinal cord. ALS is occasionally diagnosed with frontotemporal lobar dementia with ubiquitin-positive inclusions (FTLD-U). Alzheimer's disease (AD) is the most common type of age-associated dementia. Abnormal levels of aggregated Tar-DNA binding protein-43 (TDP-43) are detected in the majority of patients with ALS, FTLD and AD. We observed a significant increase (200%) in the levels of TDP-43 in cortical autopsies of late stage AD patients. Lentiviral expression of Aβ(1-42) in the rat motor cortex led to an increase in TDP-43 pathology, including up-regulation of the mature ~44kDa protein, identical to the pathological changes seen in AD. Furthermore, expression of Aβ(1-42) was associated with TDP-43 phosphorylation and accumulation in the cytosol. Clearance of Aβ with parkin prevented TDP-43 pathology. TDP-43 modifications were also observed in 3xTransgenic AD (3xTg-AD) compared to wild type mice, but these changes were attenuated in parkin-injected hippocampi, even in the presence of Tau pathology, suggesting that TDP-43 pathology is triggered by Aβ, independent of Tau. Increased levels of casein kinase (CK1 and CK2), which are associated with TDP-43 phosphorylation, were also observed in Aβ(1-42) expressing brains. These data indicate an overlap in TDP-43 pathology between AD and ALS-FTLD and suggest that Aβ triggers modifications of TDP-43.

False

CitationGPTRetr11754

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Abstract of the paper: Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.

False

CitationGPTRetr11755

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Accumulation of transactive response DNA binding protein 43 in mild cognitive impairment and Alzheimer disease. Abstract of the paper: Transactive response DNA binding protein 43 (TDP-43) plays a central role in the neuropathology of frontotemporal lobar degeneration and amyotrophic lateral sclerosis, but the relationship between TDP-43 abnormalities and Alzheimer disease (AD) remains unclear. To determine whether TDP-43 can serve as a neuropathologic marker of AD, we performed biochemical characterization and quantification of TDP-43 in homogenates from parietal neocortex of subjects with aclinical diagnosis of no cognitive impairment (NCI, n = 12), mild cognitive impairment (MCI, n = 12), or AD (n = 12). Immunoblots revealed increased detergent-insoluble TDP-43 in the cortex of 0, 3, and 6 of the 12 individuals with NCI, MCI, or AD, respectively. Detergent-insoluble TDP-43 was positively correlated with the accumulation of soluble Aβ42, amyloid plaques, and paired helical filamenttau. In contrast, phospho-TDP-43 was decreased in the cytosolic fraction and detergent-soluble membrane/nuclear fraction from AD patients and correlated with antemortem cognitive function.Immunofluorescence analysis confirmed that the frequencies of individuals with TDP-43 or phospho-TDP-43 cytoplasmic inclusions were higher in AD than in NCI, with MCI at an intermediate level. These data indicate that abnormalities of TDP-43 occur in an important subset of MCI and AD patients and that they correlate with the clinical and neuropathologic features of AD.

False

CitationGPTRetr11756

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Concurrence of TDP-43, tau and alpha-synuclein pathology in brains of Alzheimer's disease and dementia with Lewy bodies. Abstract of the paper: TAR-DNA-binding protein 43 (TDP-43) has been identified as a major component protein of ubiquitin-positive inclusions in brains from patients with frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. To obtain the precise prevalence of TDP-43 pathology in neurodegenerative disorders, we examined brains from patients with tauopathies and synucleinopathies as well as FTLD-U using immunohistochemical analysis. Consequently, TDP-43-positive inclusions within neurons and oligodendroglia were found in brains from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) in addition to FTLD-U, but not with Parkinson's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration or FTDP-17. The amygdala and hippocampus that were vulnerable to tau or alpha-synuclein pathology demonstrated more severe TDP-43 pathology in AD and DLB cases than in FTLD-U cases. In contrast, in the frontal cortex and basal ganglia that were vulnerable to TDP-43 pathology in FTLD-U, TDP-43 pathology was not observed in AD and DLB cases. Thus, the neuroanatomical distribution of TDP-43 pathology in AD and DLB cases was obviously different from that in FTLD-U cases. Furthermore, a subset of TDP-43-positive inclusions co-existed with neurofibrillary tangles (NFTs) or Lewy bodies (LBs) in the same neurons. Upon double-immunofluorescent labeling analysis, TDP-43 was hardly superimposed with tau, while TDP-43 was partially superimposed with alpha-synuclein, suggesting that neither NFTs nor LBs themselves show TDP-43 immunoreactivity and that TDP-43 pathology found in this study may be related in some way to AD and LB pathology. This study will provide a more in-depth understanding of the various pathogenic pathways leading to neurodegenerative disorders.

False

CitationGPTRetr11757

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration. Abstract of the paper: Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic features of disease. Seven cases of FTLD-TDP were identified here which were difficult to classify based on existing pathologic criteria. Distinct features common to these cases included TDP-43 aggregates over a wide neuroanatomic distribution comprised of granulofilamentous neuronal inclusions, abundant grains, and oligodendroglial inclusions. TDP-43 aggregates were phosphorylated and associated with loss of normal nuclear TDP-43 protein (nuclear clearance) but were negative for ubiquitin. Biochemical analysis confirmed the presence of insoluble and phosphorylated TDP-43 and also revealed a distinct pattern of TDP-43 C-terminal fragments relative to other FTLD-TDP subtypes. Finally, these cases were uniformly associated with a very rapid clinical course culminating in death within ~3 years of disease onset. We suggest that these cases may represent a unique clinicopathologic subtype of FTLD-TDP which we provisionally call "type E." The immature appearance of TDP-43 aggregates, widespread distribution, uniform biochemical profile and rapid clinical course highlights the clinical and pathologic variability within FTLD-TDP, and raises the possibility that type E neuropathology is the sequelae of a particularly virulent strain of TDP-43 proteinopathy.

False

CitationGPTRetr11758

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Abstract of the paper: TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD with or without MND. On selected cases, immunoelectron microscopy and biochemistry were performed. Clinically defined frontotemporal dementias (FTDs) included four groups: 1) familial FTD with mutations in progranulin (n = 36), valosin-containing protein (n = 5), charged multivesicular body protein 2B (n = 4), and linked to chromosome 9p (n = 7); 2) familial cases of FTD with unknown gene association (n = 29); 3) sporadic FTD (n = 72); and 4) familial and sporadic FTD with MND (n = 40). Our studies confirm that the spectrum of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FTD with charged multivesicular body protein 2B mutations. Thus, despite significant clinical, genetic, and neuropathological heterogeneity of FTLD-U, TDP-43 is a common pathological substrate underlying a large subset of these disorders, thereby implicating TDP-43 in novel and unifying mechanisms of FTLD pathogenesis.

False

CitationGPTRetr11759

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: given the pathological observations that a proportion of patients with ad 1 or ftld harbour tdp43 pathological changes within their brains it can be hypothesised that similar proportions of patients might show altered blood or plasma levels of tdp43 and that this could be a useful biomarker of the presence of tdp43 brain pathology Title of the paper: TDP-43: a novel neurodegenerative proteinopathy. Abstract of the paper: Over the past decade, it has become clear that there is a significant overlap in the clinical spectrum of frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). The identification of TDP-43 as the major disease protein in the pathology of both frontotemporal lobar degeneration with ubiquitin inclusions and ALS provides the first molecular link for these diseases. Pathological TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved to generate carboxy-terminal fragments in affected brain regions. The normal nuclear expression of TDP-43 is also reduced leading to the hypothesis that sequestration of TDP-43 in pathological inclusions contributes to disease pathogenesis. Thus, TDP-43 is the newest member of the growing list of neurodegenerative proteinopathies, but unique in that it lacks features of brain amyloidosis.

False

CitationGPTRetr11760

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Neuron Loss in Alzheimer's Disease: Translation in Transgenic Mouse Models. Abstract of the paper: Transgenic mouse models represent an essential tool for the exploration of Alzheimer's disease (AD) pathological mechanisms and the development of novel treatments, which at present provide only symptomatic and transient effects. While a variety of mouse models successfully reflects the main neuropathological hallmarks of AD, such as extracellular amyloid-β (Aβ) deposits, intracellular accumulation of Tau protein, the development of micro- and astrogliosis, as well as behavioral deficits, substantial neuron loss, as a key feature of the disease, seems to be more difficult to achieve. In this review, we summarize information on classic and more recent transgenic mouse models for AD, focusing in particular on loss of pyramidal, inter-, and cholinergic neurons. Although the cause of neuron loss in AD is still a matter of scientific debate, it seems to be linked to intraneuronal Aβ accumulation in several transgenic mouse models, especially in pyramidal neurons.

False

CitationGPTRetr11761

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Neuron loss in transgenic mouse models of Alzheimer's disease. Abstract of the paper: Since their initial generation in the mid 1990s, transgenic mouse models of Alzheimers's disease (AD) have been proven to be valuable model systems which are indispensable for modern AD research. Whereas most of these models are characterized by extensive amyloid plaque pathology, inflammatory changes and often behavioral deficits, modeling of neuron loss was much less successful. The present paper discusses the current achievements of modeling neuron loss in transgenic mouse models based on APP/Aβ and Tau overexpression and provides an overview of currently available AD mouse models showing these pathological alterations.

False

CitationGPTRetr11762

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Selective loss of basal forebrain cholinergic neurons in APP770 transgenic mice. Abstract of the paper: OBJECTIVE To determine whether cholinergic neurons in the basal nucleus magnocellularis (NBM) and the medial septum are affected in transgenic mice overexpressing human amyloid precursor protein 770 (APP770). METHODS Eight age groups, from 3 months old to 10 months old, of either heterozygous transgenic or non-transgenic mice were used for choline acetyltransferase (ChAT) staining using immunohistochemistry. The number of ChAT-positive neurons was counted on the MCID Image Analysis System. Neurons in the cerebral cortex and area CA1 of hippocampus were also stained with cresyl violet and counted using optical dissector technique. RESULTS There is no change in the number of forebrain cholinergic neurons in the transgenic mice up to 9 months of age. A loss of these cholinergic neurons starts in 9 months old transgenic mice, with a further decrease in the number of NBM and medial septum neurons in 10-month-old transgenic mice. On the other hand, the number of neurons in the cerebral cortex and hippocampal area CA1 remained unchanged. CONCLUSION These results demonstrate a selective loss of basal forebrain cholinergic neurons in APP770 transgenic mice.

False

CitationGPTRetr11763

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease. Abstract of the paper: According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L). Stereologic and image analyses revealed substantial age-related neuron loss in the hippocampal pyramidal cell layer of APP/PS-1 double-transgenic mice. The loss of neurons was observed at sites of Abeta aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques. These findings point to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer's disease.

False

CitationGPTRetr11764

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Age-related loss of noradrenergic neurons in the brains of triple transgenic mice. Abstract of the paper: Microscopic findings in Alzheimer's disease (AD) at autopsy include a wide cortical distribution of beta amyloid (Aβ)-containing plaques and diminished numbers of pyramidal neurons in CA1 of hippocampus and tyrosine hydroxylase-positive (TH+) neurons in the locus coeruleus (LC). To better understand the neuropathology underlying cognitive decline in AD, we analyzed the AD-type neuropathology in brains of triple transgenic (3×Tg) mice harboring mutations for APP(swe), PS1(M146V), and tau(P301L). Histochemical and immunohistochemical staining and computerized stereology were carried out in age-matched young, early middle age, and late middle age 3×Tg mice. The 3×Tg mice showed an intracellular Aβ deposition in subiculum and CA1 pyramidal neurons and an extracellular distribution of amyloid plaques specifically in the subiculum of hippocampal formation and in neocortical layer V. The 3×Tg mice also showed an age-related loss of TH+ neurons in LC, with a loss of 37% of these neurons at 15 months of age. There was no loss of CA1 neurons at any age examined. Reduced AD-type neuropathology in CA1 of 3×Tg mice suggests a possible neuroprotective role for high intracellular-to-extracellular ratios of insoluble Aβ deposits. Understanding the neurobiology of this apparent neuroprotection could lead to an improved understanding of age-related cognitive function in general, and the development of novel strategies for the therapeutic management of AD patients.

False

CitationGPTRetr11765

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Mouse models of Alzheimer's disease: insight into treatment. Abstract of the paper: Mice overexpressing mutant Alzheimer's disease (AD)-related proteins exhibit many of the neuropathological and behavioral features of the human disease. Transgenic animals have been created that express mutations in the amyloid precursor protein (APP), presenilin (PS)1, and PS2, and also animals expressing more than one of these mutations. For example, in APP mouse models, there are age-related accumulations of amyloid-beta (Abeta)-containing neuritic plaques in the hippocampus and cerebral cortex, activation of astrocytes and microglial cells in regions containing plaques, and degeneration of cholinergic nerve terminals in brain regions that eventually become plaque containing. Missing in the APP and PS mouse models are neurofibrillary tangles and robust neuronal loss in cerebral cortical and subcortical regions such as the basal forebrain cholinergic and locus coeruleus noradrenergic nuclei. Neurofibrillary tangles can be produced in mice expressing mutant tau protein, and the tangle formation is further enhanced in animals that also express mutant APP. Studies in APP mouse models indicate that, like AD, there are abnormalities in adult hippocampal neurogenesis. The animal models of AD have been used to develop and test treatments that reduce brain levels of the Abeta42 protein, neuritic plaque load and glial activation, and some have been found to restore learning and memory function. If such treatments can be shown to stop the neurodegenerative process and restore hippocampal neurogenesis, damaged brain circuits may be replaceable in patients with AD.

True

CitationGPTRetr11766

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Review: Neuropathology and behavioural features of transgenic murine models of Alzheimer's disease. Abstract of the paper: Our understanding of the underlying biology of Alzheimer's disease (AD) has been steadily progressing; however, this is yet to translate into a successful treatment in humans. The use of transgenic mouse models has helped to develop our understanding of AD, not only in terms of disease pathology, but also with the associated cognitive impairments typical of AD. Plaques and neurofibrillary tangles are often among the last pathological changes in AD mouse models, after neuronal loss and gliosis. There is a general consensus that successful treatments need to be applied before the onset of these pathologies and associated cognitive symptoms. This review discusses the different types of AD mouse models in terms of the temporal progression of the disease, how well they replicate the pathological changes seen in human AD and their cognitive defects. We provide a critical assessment of the behavioural tests used with AD mice to assess cognitive changes and decline, and discuss how successfully they correlate with cognitive impairments in humans with AD. This information is an important tool for AD researchers when deciding on appropriate mouse models, and when selecting measures to assess behavioural and cognitive change.

False

CitationGPTRetr11767

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Learning and memory in transgenic mice modeling Alzheimer's disease. Abstract of the paper: Recent advances in behavioral analyses of transgenic mouse models of Alzheimer's disease (AD) are discussed, and their impact on our understanding of the molecular basis of cognitive impairment in AD is considered. Studies of the relationship between memory and A Beta in transgenic mice expressing the amyloid precursor protein (APP) and its variants suggest that aging promotes the formation of soluble A Beta assemblies mediating negative effects on memory. A significant component of memory loss in APP transgenic mice is apparently caused by soluble A Beta assemblies, but whether and how much of the dementia within individuals afflicted with AD is caused by these A Beta species is unclear. Future studies in composite transgenic mice developing amyloid plaques, neurofibrillary tangles, and other AD pathology may allow for the determination of the relative contribution of A Beta and non-A Beta components to dementia.

False

CitationGPTRetr11768

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Selecting a mouse model of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disease and cause of dementia. Significant strides toward understanding and developing therapies for AD have been supported by the use of transgenic mouse models of AD. Over the last two decades, a number of mouse models have been created to recapitulate the major neuropathological hallmarks of the disease, namely amyloid plaques and neurofibrillary tangles. These mice recapitulate many, although not all, of the key features of AD, and have been widely used in AD research. At the present time, there are numerous types of transgenic mice available for the study of AD, many of which have been characterized to some extent in terms of neuronal, neuropathological, and/or behavioral abnormalities. This repository of transgenic mice offers a wealth of opportunity to investigate the cellular mechanisms underlying AD, and the choice of mouse model for research should be guided by the specific questions to be answered. We provide here some considerations for selecting a mouse model of AD best suited to particular lines of investigation.

False

CitationGPTRetr11769

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. Abstract of the paper: Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model. Expression of the APP transgene was found in ChAT-positive neurons of motor nuclei accompanied by robust intracellular Abeta accumulation, whereas no APP expressing neurons and thus no intracellular Abeta accumulation were found in neither the forebrain or pons complexes, nor in the caudate putamen. This expression pattern was used as a model system to study the effect of intra- and extracellular Abeta accumulation on neuron loss in the cholinergic system. Stereological quantification revealed a loss of ChAT-positive neurons in APP/PS1KI mice only in the motor nuclei Mo5 and 7N accumulating intracellular Abeta. This study supports the hypothesis of intracellular Abeta accumulation as an early pathological alteration contributing to cell death in AD.

False

CitationGPTRetr11770

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Basal forebrain neurons in the dementia of Parkinson disease. Abstract of the paper: Demented patients with Parkinson disease share certain neuropathological and neurochemical features with patients suffering from Alzheimer disease. Recently, loss of cholinergic neurons in the basal forebrain, particularly the nucleus basalis of Meynert, has been implicated in the pathophysiology of Alzheimer disease. The present investigations of 12 patients with Parkinson disease demonstrates that the demented patients with this disease also show a selective loss of cells in the nucleus basalis of Meynert, thus providing an important link between the dementias of Alzheimer disease and Parkinson disease.

True

CitationGPTRetr11771

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Transgenic mouse models of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by a progressive loss of cognitive function. Despite considerable progress, a complete description of the molecular pathology of this disease has yet to be elucidated. In this respect, the need for an animal model that develops some or all aspects of this uniquely human disease in a reproducible fashion is crucial for the development and testing of potential treatments. A valid animal model for AD should exhibit (1) progressive AD-like neuropathology and (2) cognitive deficits, and (3) should be verified in several laboratories. Transgenic models should be able to (4) discern pathogenic effects of familial forms (FAD) mutations from those of transgene overexpression. Models derived from microinjection of FAD mutant alleles should (5) encompass more than one Tg line. At present, however, no model that replicates all of these desirable features exists. In this review, we discuss transgenic mouse models with well-characterized AD-like neuropathology that show some form of cognitive impairment. We argue that conclusions drawn from a limited selection of cross-sectional experiments should be verified in longitudinally designed experiments. Future studies should attempt to establish a closer relationship between molecular pathology and the degree of cognitive impairment. While exact replication of AD in mice may not attainable (due to phylogenetic differences and fundamental differences in behavioral ecology), rigorous comparative analysis of cognitive behavior observed in various mouse models of AD should provide a framework for better understanding of molecular mechanisms underlying cognitive impairment observed in AD patients.

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CitationGPTRetr11772

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Transgenic mice expressing Alzheimer amyloid precursor proteins. Abstract of the paper: Nearly a decade after the identification of the Alzheimer amyloid precursor protein (APP) gene several groups of investigators have created transgenic mice expressing APP that simulate some of the prominent behavioral and pathological features of Alzheimer's disease (Quon et al., 1991; Games et al., 1995; Hsiao et al., 1995, 1996; Moechars et al., 1996; Sturchler-Pierrat et al., 1997). These features, which are present to various degrees in different lines of mice, include age-related impairment in learning and memory, neuronal loss, gliosis, neuritic changes, amyloid deposition, and abnormal tau phosphorylation. No mouse model exhibiting every neuropathological feature of Alzheimer's disease exists. Whether an exact simulation of Alzheimer neuropathology is required to understand neural dysfunction in Alzheimer's disease is unclear. Various mouse models of Alzheimer's disease are summarized in this article.

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CitationGPTRetr11773

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. Abstract of the paper: APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. We have previously reported neuron loss in the hippocampal CA1 region of 14- to 18-month-old APP23 mice. In contrast, no neuron loss was found in neocortex. In the present study we have reinvestigated neocortical neuron numbers in adult and aged APP23 mice. Surprisingly, results revealed that 8-month-old APP23 mice have 13 and 14% more neocortical neurons compared with 8-month-old wild-type and 27-month-old APP23 mice, respectively. In 27-month-old APP23 mice we found an inverse correlation between amyloid load and neuron number. These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. Supporting this notion, we found more neurons with a necrotic-apoptotic phenotype in the neocortex of 24-month-old APP23 mice compared with age-matched wild-type mice. Stimulated by recent reports that demonstrated neurogenesis after targeted neuron death in the mouse neocortex, we have also examined neurogenesis in APP23 mice. Strikingly, we found a fourfold to sixfold increase in newly produced cells in 24-month-old APP23 mice compared with both age-matched wild-type mice and young APP23 transgenic mice. However, subsequent cellular phenotyping revealed that none of the newly generated cells in neocortex had a neuronal phenotype. The majority were microglial and to a lesser extent astroglial cells. We conclude that cerebral amyloidosis in APP23 mice causes a modest neuron loss in neocortex and induces marked gliogenesis.

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CitationGPTRetr11774

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.

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CitationGPTRetr11775

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Transgenic mouse models of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) pathology is characterized by A beta peptide-containing plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, extensive neuritic degeneration, and distinct neuron loss. We generated several transgenic mouse lines expressing the human amyloid precursor protein (APP751) containing the AD-linked KM670/671NL double mutation (Swedish mutation) under the control of a neuron-specific Thy-1 promoter fragment. In the best APP-expressing line (APP23), compact A beta deposits can be detected at 6 months of age. These plaques dramatically increase with age, are mostly Congo Red positive, and accumulate typical plaque-associated proteins such as heparansulfate proteoglycan and apolipoprotein E. Activated astrocytes and microglia indicative of inflammatory processes reminiscent of AD accumulate around the deposits. Furthermore, plaques are surrounded by enlarged dystrophic neurites as visualized by neurofilament or Holmes-Luxol staining. Strong staining for acetylcholinesterase activity is found throughout the plaques and is accompanied by local distortion of the cholinergic fiber network. All congophilic plaques contain hyperphosphorylated tau reminiscent of early tau pathology. Modern stereologic methods demonstrate a significant loss of neurons in the hippocampal CA1 region, correlating with an increasing A beta plaque load. Interestingly, APP23 mice develop cerebral amyloid angiopathy in addition to amyloid plaques even though the APP transgene is only expressed in neurons. Crossbreeding of APP23 mice with transgenic mice carrying AD-linked presenilin mutations but not wild-type presenilin resulted in enhanced formation of pathology. In conclusion, our APP transgenic mice present many pathologic features, similar to those observed in AD and therefore offer excellent tools for studying the contribution of A beta to AD pathogenesis.

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CitationGPTRetr11776

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Plaques, tangles, and memory loss in mouse models of neurodegeneration. Abstract of the paper: Within the past decade, our understanding of the pathogenic mechanisms in Alzheimer's disease (AD) has dramatically advanced because of the development of transgenic mouse models that recapitulate the key pathological and behavioral phenotypes of the disease. These mouse models have allowed investigators to test detailed questions about how pathology develops and to evaluate potential therapeutic approaches that could slow down the development of this disease. In this review, we discuss the status of transgenic mouse models and review the complex relationship between pathology and behavior in the development of neuropathological syndromes in AD.

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CitationGPTRetr11777

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Cholinergic neuropathology in a mouse model of Alzheimer's disease. Abstract of the paper: Transgenic mice overexpressing mutant human amyloid precursor protein (PDAPP mice) develop several Alzheimer's disease (AD)-like lesions including an age-related accumulation of amyloid-beta (Abeta)-containing neuritic plaques. Although aged, heterozygous PDAPP mice also exhibit synaptic and glial cell changes characteristic of AD pathology, no evidence of widespread neuronal loss has been observed. The present study sought to determine whether homozygous PDAPP mice, which express very high levels of Abeta peptide, exhibit AD-like cholinergic degenerative changes, and whether the changes parallel the deposition of Abeta plaques. Mice were examined at 2 and 4 months and at 1 and 2 years of age. There was an age-related increase in the density of Abeta plaques in the cortex and hippocampus of the PDAPP animals; at 4 months of age there were very few plaques, and at 2 years there was a very high density of plaques. There was an age-related reduction in the density of cholinergic nerve terminals in the cerebral cortex; at 2 months there was a normal density of nerve terminals, but as early as age 4 months there was an approximately 50% reduction. However, at age 2 years there was no difference in the number or size of basal forebrain cholinergic somata compared with 2-month-old PDAPP mice. These data indicated that the homozygous PDAPP mouse exhibits cholinergic nerve terminal degenerative pathology and that the cortical neurodegenerative changes occur before the deposition of Abeta-containing neuritic plaques.

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CitationGPTRetr11778

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. Abstract of the paper: Alzheimer's Disease (AD) is a neurodegenerative disorder that is characterized by extracellular deposits of amyloid-beta peptide (Abeta) and a severe depletion of the cholinergic system, although the relationship between these two events is poorly understood. In the neocortex, there is a loss of cholinergic fibers and receptors and a decrease of both choline acetyltransferase (ChAT) and acetylcholinesterase enzyme activities. The nucleus basalis of Meynert (NBM), which provides the major cholinergic input to the neocortex, undergoes profound neuron loss in AD. In the present study, we have examined the cholinergic alterations in amyloid precursor protein transgenic mice (APP23), a mouse model of cerebral beta-amyloidosis. In aged APP23 mice, our results reveal modest decreases in cortical cholinergic enzyme activity compared with age-matched wild-type mice. Total cholinergic fiber length was more severely affected, with 29 and 35% decreases in the neocortex of aged APP23 mice compared with age-matched wild-type mice and young transgenic mice, respectively. However, there was no loss of cholinergic basal forebrain neurons in these aged APP23 mice, suggesting that the cortical cholinergic deficit in APP23 mice is locally induced by the deposition of amyloid and is not caused by a loss of cholinergic basal forebrain neurons. To study the impact of cholinergic basal forebrain degeneration on cortical amyloid deposition, we performed unilateral NBM lesions in adult APP23 mice. Three to 8 months after lesioning, a 38% reduction in ChAT activity and significant cholinergic fiber loss were observed in the ipsilateral frontal cortex. There was a 19% decrease in Abeta levels of the ipsilateral compared with contralateral frontal cortex with no change in the ratio of Abeta40 to Abeta42. We conclude that the severe cholinergic deficit in AD is caused by both the loss of cholinergic basal forebrain neurons and locally by cerebral amyloidosis in the neocortex. Moreover, our results suggest that disruption of the basal cholinergic forebrain system does not promote cerebral amyloidosis in APP23 transgenic mice.

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CitationGPTRetr11779

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: cell loss affecting basal forebrain cholinergic areas observed in patients with ad 330 has not been reported in transgenic mice 125 reviewed in 102 except in the trisomy 21 model trisomy 16 in the mouse Title of the paper: Overview of Transgenic Mouse Models for Alzheimer's Disease. Abstract of the paper: This review describes several transgenic mouse models of Alzheimer's disease (AD), a devastating neurodegenerative disorder that causes progressive cognitive decline and is diagnosed postmortem by the presence of extracellular amyloid-β (Aβ) plaques and intraneuronal tau neurofibrillary tangles in the cerebral cortex. Currently there is no intervention that cures, prevents, or even slows disease progression. Its complex etiology and pathology pose significant challenges for animal model development, and there is no single model that faithfully recapitulates both the pathological aspects and behavioral phenotypes of AD. Nearly 200 transgenic rodent models of AD have been generated primarily based on mutations linked to Aβ protein misprocessing in the familial form of the disease. More recent models incorporate mutations in tau protein, as well as mutations associated with the sporadic form of the disease. The salient features, strengths, limitations, and key differentiators for the most commonly used and best characterized of these models are considered here. While the translational utility of many of these models to assess the potential of novel therapeutics is in dispute, knowledge of the different models available and a detailed understanding of their features can aid in the selection of the optimal model to explore disease mechanisms or evaluate candidate medications. We comment on the predictive utility of these models considering recent clinical trial failures and discuss trends and future directions in the development of models for AD based on the plethora of clinical data that have been generated over the last decade. © 2019 by John Wiley & Sons, Inc.

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