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CitationGPTRetr11500

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: BACKGROUND Diffusion tensor imaging (DTI) studies have shown significant cross-sectional differences among normal controls (NC) mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients in several fiber tracts in the brain, but longitudinal assessment is needed. METHODS We studied 75 participants (25 NC, 25 amnestic MCI, and 25 mild AD) at baseline and 3 months later, with both imaging and clinical evaluations. Fractional anisotropy (FA) was analyzed in regions of interest (ROIs) in: (1) fornix, (2) cingulum bundle, (3) splenium, and (4) cerebral peduncles. Clinical data included assessments of clinical severity and cognitive function. Cross-sectional and longitudinal differences in FA, within each ROI, were analyzed with generalized estimating equations (GEE). RESULTS Cross-sectionally, AD patients had lower FA than NC (p<0.05) at baseline and 3 months in the fornix and anterior portion of the cingulum bundle. Compared to MCI, AD cases had lower FA (p<0.05) in these regions and the splenium at 0 and 3 months. Both the fornix and anterior cingulum correlated across all clinical cognitive scores; lower FA in these ROIs corresponded to worse performance. Over the course of 3 months, when the subjects were clinically stable, the ROIs were also largely stable. CONCLUSIONS Using DTI, findings indicate FA is decreased in specific fiber tracts among groups of subjects that vary along the spectrum from normal to AD, and that this measure is stable over short periods of time. The fornix is a predominant outflow tract of the hippocampus and may be an important indicator of AD progression.

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CitationGPTRetr11501

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis study. Abstract of the paper: Alzheimer's disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.

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CitationGPTRetr11502

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Diffusion tensor imaging in Alzheimer's disease: insights into the limbic-diencephalic network and methodological considerations. Abstract of the paper: Glucose hypometabolism and gray matter atrophy are well known consequences of Alzheimer's disease (AD). Studies using these measures have shown that the earliest clinical stages, in which memory impairment is a relatively isolated feature, are associated with degeneration in an apparently remote group of areas-mesial temporal lobe (MTL), diencephalic structures such as anterior thalamus and mammillary bodies, and posterior cingulate. These sites are thought to be strongly anatomically inter-connected via a limbic-diencephalic network. Diffusion tensor imaging or DTI-an imaging technique capable of probing white matter tissue microstructure-has recently confirmed degeneration of the white matter connections of the limbic-diencephalic network in AD by way of an unbiased analysis strategy known as tract-based spatial statistics (TBSS). The present review contextualizes the relevance of these findings, in which the fornix is likely to play a fundamental role in linking MTL and diencephalon. An interesting by-product of this work has been in showing that alterations in diffusion behavior are complex in AD-while early studies tended to focus on fractional anisotropy, recent work has highlighted that this measure is not the most sensitive to early changes. Finally, this review will discuss in detail several technical aspects of DTI both in terms of image acquisition and TBSS analysis as both of these factors have important implications to ensure reliable observations are made that inform understanding of neurodegenerative diseases.

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CitationGPTRetr11503

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Disruption of thalamic connectivity in Alzheimer's disease: a diffusion tensor imaging study. Abstract of the paper: The aim of this study was to evaluate the structural integrity of the thalamic connectivity of specific fiber tracts in different stages of Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Thirty-five patients with AD and 22 normal control (NC) subjects were recruited. Based on Mini Mental State Examination score, the AD patients were divided into three subgroups for comparison with the NC group: mild (mi-AD, n = 14), moderate (mo-AD, n = 12), and severe (se-AD, n = 9) AD. The fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR) were selected to represent the thalamic connectivity with other brain regions. The fornix was divided into the column and body of the fornix (FX-1) and the bilateral fornix (crus)/stria terminalis (FX-2/ST) based on the atlas. Through the atlas-based analysis and fiber tracking method, we measured fractional anisotropy (FA), mean diffusivity (MD), and tract volume to reflect the microstructural and macrostructural changes of these fibers during AD progression. There were significant differences in the FA and MD of all fibers, except the right PTR, between the AD and NC subjects. Further subgroup analyses revealed that the mi-AD subgroup had decreased FA only in the FX-1 and increased MD in the FX-1 and bilateral ATR, the mo-AD subgroup showed declined FA and increased MD in the FX-1, bilateral FX-2/ST and ATR; the se-AD subgroup exhibited lower FA and higher MD values in all fibers except the right PTR. We also found reduced tract volume values in the FX and left ATR in the AD patients. Further subgroup analyses revealed that these differences only existed in the se-AD patients. Our DTI analyses indicate that the integrity of thalamic connectivity is progressively disrupted following cognitive decline in AD and that DTI parameters in the column and body of the fornix show promise as potential markers for the early diagnosis of AD and for monitoring disease progression.

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CitationGPTRetr11504

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Assessment of white matter tract damage in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: Diffusion tensor MRI-based tractography was used to investigate white matter (WM) changes in the major limbic (i.e., fornix and cingulum) and cortico-cortical association pathways [i.e., the uncinate fasciculus, the inferior fronto-occipital fasciculus, the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus, and the corpus callosum] in 25 Alzheimer's disease (AD) patients, 19 amnestic mild cognitive impairment (aMCI) patients, and 15 healthy controls (HC). Mean diffusivity (MD), fractional anisotropy (FA), as well as axial (DA) and radial (DR) diffusivities were measured for each tract, using an atlas-based tractography approach. The association of WM tract integrity with hippocampal volume was also assessed. MD values were significantly different among groups in all WM tracts (P values ranging from 0.002 to 0.03), except in the fornix (P = 0.06) and the inferior fronto-occipital fasciculus (P = 0.09). Conversely, FA was significantly different among groups in the fornix only (P = 0.02). DA values were significantly different among groups in all WM tracts (P values ranging from 0.001 to 0.01), except in the fornix (P = 0.13) and the cingulum (P = 0.29). Significantly different DR values among groups were found in the fornix (P = 0.02) and the ILF (P = 0.01). In the fornix and cingulum, DR was significantly more increased than DA in both patient groups compared to HC. No difference in DA versus DR was found in cortico-cortical WM tracts. DA values in the fornix were significantly correlated with the hippocampal volume. This study demonstrates a different pattern of WM involvement in the limbic and cortico-cortical association pathways in aMCI and AD patients.

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CitationGPTRetr11505

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Diffusion tensor imaging in Alzheimer disease and mild cognitive impairment. Abstract of the paper: A wide range of imaging studies provides growing support for the potential role of diffusion tensor imaging (DTI) in evaluating microstructural white matter integrity in Alzheimer disease (AD) and mild cognitive impairment (MCI). Our review aims to present DTI principles, post-processing and analysis frameworks and to report the results of particular studies. The distribution of AD-related white matter abnormalities is widely discussed in the light of deteriorated connectivity within certain tracts due to secondary white matter degeneration; primary alterations are also assumed to contribute to the pattern. The question whether it is more effective to assess the whole-brain diffusion or to directly concentrate on specific regions remains an interesting issue. Assessing white matter microstructure alterations, as evaluated by group-level differences of tensor-derived parameters, may be a promising neuroimaging tool for differential diagnosis between AD, MCI and other cognitive disorders, as well as being particularly helpful in the interpretation of underlying pathological processes.

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CitationGPTRetr11506

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Quantitative MRI to understand Alzheimer's disease pathophysiology. Abstract of the paper: PURPOSE OF REVIEW The role of white matter damage in the progression of Alzheimer's disease and the associated cognitive symptoms is becoming increasingly clearer. This is partly because of the advent of diffusion tensor imaging, which, in combination with other quantitative MRI techniques, offers unique insights into the patholophysiology of Alzheimer's disease in vivo. The purpose of this review is to integrate the most recent imaging findings, with respect to understanding Alzheimer's disease pathophysiology, and identifying potential biomarkers with diagnostic and prognostic value. RECENT FINDINGS Consistent with patterns of gray matter atrophy, white matter damage in Alzheimer's disease is localized within white matter tracts connecting the temporal lobe with the rest of the brain, including the cingulum, the uncinate fasciculus and the fornix. These abnormalities are often correlated with adjacent gray matter tissue loss, and with cognitive performance. The relationship between these findings and loss of functional connectivity supports the hypothesis of disconnection as a mechanism for the spread of Alzheimer's disease. SUMMARY White matter abnormalities occur early in Alzheimer's disease, and might actively contribute to the progression of the disease. Functional and structural gray matter abnormalities parallel the white matter changes, and successful biomarkers are likely to be multiparametric.

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CitationGPTRetr11507

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Diffusion characteristics of the fornix in patients with Alzheimer's disease. Abstract of the paper: White matter degradation is a major part of the pathogenesis of Alzheimer's disease (AD). The fornix is the predominant outflow tract from the hippocampus, and alterations to its microstructure in patients with AD are still being explored. Diffusion tensor imaging (DTI) is an in vivo neuroimaging technique that can provide unique information about alterations in tissue microstructure, which can indicate underlying neurobiological process at the microstructural level. In this prospective study, DTI was used to assess and analyze the microstructural features of the fornix in subjects with AD (n = 17), mild cognitive impairment (MCI; n = 12) and healthy controls (n = 17). DTI was performed using Explore DTI software and the FSL package. Within the fornix, patients with AD showed decreased fractional anisotropy values and length of fiber tracts of the fornix relative to healthy controls, but higher mean diffusivity values. MCI subjects showed a trend towards elevated mean diffusivity values in the fornix. The data suggest that DTI provides supporting information on the microstructural alteration of the fornix in patients with AD, and that these diffusion characteristics of the fornix may be helpful for the clinical diagnosis of AD.

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CitationGPTRetr11508

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. Abstract of the paper: A novel MRI method--diffusion tensor imaging--was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance.

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CitationGPTRetr11509

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: BACKGROUND Diffusion tensor imaging (DTI) is a promising method for identifying significant cross-sectional differences of white-matter tracts in normal controls (NC) and those with mild cognitive impairment (MCI) or Alzheimer's disease (AD). There have not been many studies establishing its longitudinal utility. METHODS Seventy-five participants (25 NC, 25 amnestic MCI, and 25 AD) had 3-Tesla MRI scans and clinical evaluations at baseline and 3, 6, and 12 months. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed at each time-point and longitudinally in eight a priori-selected areas taken from four regions of interest (ROIs). RESULTS Cross-sectionally, MD values were higher, and FA values lower in the fornix and splenium of the AD group compared with either MCI or NC (P < .01). Within-group change was more evident in MD than in FA over 12 months: MD increased in the inferior, anterior cingulum, and fornix in both the MCI and AD groups (P < .01). CONCLUSIONS There were stable, cross-sectional, region-specific differences between the NC and AD groups in both FA and MD at each time-point over 12 months. Longitudinally, MD was a better indicator of change than FA. Significant increases of fornix MD in the MCI group suggest this is an early indicator of progression.

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CitationGPTRetr11510

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Gray and white matter changes in Alzheimer's disease: a diffusion tensor imaging study. Abstract of the paper: PURPOSE To investigate microstructural changes in cortical and white matter pathways in patients with Alzheimer's disease using diffusion tensor imaging (DTI). MATERIALS AND METHODS Measures of mean diffusivity (MD) and fractional anisotropy (FA) were compared in the brains of 13 Alzheimer's disease (AD) patients and a group of 13 aged-matched control participants employing an optimized DTI technique involving a fully automated, voxel-based morphometric (VBM) analysis. RESULTS After rigorous control for anatomical variation and confounding partial volume effects, we found significantly elevated MD measures within the hippocampus, amygdala, and medial temporal, parietal, and frontal lobe gray matter regions in the AD participants. The largest number of pixels with increased MD was localized bilaterally, within the posterior cingulate gyrus. The FA was significantly reduced within the thalamus, parietal white matter, and posterior limbs of the internal capsule, indicating significant involvement of corticothalamic and thalamocortical radiations. CONCLUSION This study demonstrates that rigorous VBM analysis of DTI data can be used to investigate microstructural changes in cortical, subcortical, and white matter regions in AD.

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CitationGPTRetr11511

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: The fornix sign: a potential sign for Alzheimer's disease based on diffusion tensor imaging. Abstract of the paper: BACKGROUND We investigated a simple imaging sign for Alzheimer's disease (AD), using diffusion tensor imaging (DTI). We hypothesized that a reduction in fractional anisotropy (FA) in the fornix could be utilized as an imaging sign. METHODS Twenty-three patients with AD, 24 patients with amnestic mild cognitive impairment (aMCI), and 25 control participants (NC) underwent DTI at baseline and 1 year later. The diagnosis was reevaluated 1 year and 3 years after the initial scan. A color-scaled FA map was used to visually identify the FA reduction ("fornix sign"). We investigated whether the fornix sign could separate AD from NC, and could predict progression from aMCI to AD or NC to aMCI. We also quantified FA of the fornix to validate the fornix sign. RESULTS The fornix sign was identical to the lack of any voxels with an FA > .52 within the fornix. The fornix sign differentiated AD from NC with specificity of 1.0 and sensitivity of .56. It predicted conversion from NC to aMCI with specificity of 1.0 and sensitivity of .67, and from aMCI to AD with specificity of .94 and sensitivity of .83. CONCLUSION The fornix sign is a promising predictive imaging sign of AD.

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CitationGPTRetr11512

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study. Abstract of the paper: Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.

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CitationGPTRetr11513

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: The pattern of diffusion parameter changes in Alzheimer's disease, identified by means of linked independent component analysis. Abstract of the paper: Several recent studies have indicated that white matter is affected in Alzheimer's disease (AD). Diffusion tensor imaging is a tool by which the white matter microstructure can be examined in vivo, and might offer a possibility for the identification of the pattern of white matter disintegration in AD. In the current analysis, we made use of a novel model-free analysis approach of linked independent component analysis to identify a motif of diffusion parameter alterations exemplifying AD. Analysis of the diffusion data of 16 AD patients and 17 age-matched healthy subjects revealed six independent components, two of which demonstrated differences between the patients and controls. Component #0 was dominated by axial diffusivity, but significant alterations in fractional anisotropy and mean and radial diffusivity were also detected. Alterations were found in regions of crossing of major white matter pathways, such as forceps, corona radiate, and superior longitudinal fascicle, as well as medio-temporal white matter. These results lend support to the coexistence of white matter disintegration of the late myelinating associating fibers and wallerian degeneration-related disintegration, in accordance with the retrogenesis and wallerian degeneration hypothesis.

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CitationGPTRetr11514

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes. Abstract of the paper: Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer's disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.

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CitationGPTRetr11515

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Diffusion tensor imaging reveals visual pathway damage in patients with mild cognitive impairment and Alzheimer's disease. Abstract of the paper: Visual deficits are commonly seen in patients with Alzheimer's disease (AD), but postmortem histology has not found substantial damage in visual cortex regions, leading to the hypothesis that the visual pathway, from eye to the brain, may be damaged in AD. Diffusion tensor imaging (DTI) has been used to characterize white matter abnormalities. However, there is a lack of data examining the optic nerves and tracts in patients with AD. In this study, we used DTI to analyze the visual pathway in healthy controls, patients with mild cognitive impairment (MCI) and AD using scans provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found significant increases in the total diffusivity and radial diffusivity and reductions in fractional anisotropy in optic nerves among AD patients. Similar but less extensive changes in these metrics were seen in MCI patients as compared to controls. The differences in DTI metrics between groups mirrored changes in the splenium of the corpus callosum, which has commonly been shown to exhibit white matter damage during AD and MCI. Our findings indicate that white matter damage extends to the visual system, and may help explain the visual deficits experienced by AD patients.

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CitationGPTRetr11516

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging. Abstract of the paper: Alzheimer disease (AD) is pathologically characterized by cortical atrophy. Changes in the white matter and their relation to the pathogenesis of AD remain to be studied. To quantitatively investigate the integrity and organization of white matter fiber tracts in patients with AD, we used diffusion tensor (DT) imaging to study the diffusion anisotropy of white matter regions. DT imaging was performed using a 3.0 Tesla magnetic resonance scanner in ten probable AD patients with no or only mild changes in the white matter in T2 weighted magnetic resonance imagings and ten group-matched controls. The values of fractional anisotropy were significantly lower in the temporal subcortical white matter, posterior part of the corpus callosum, and anterior and posterior cingulate bundles in patients with AD compared with controls. Possible relationships of these selective impairments in the white matter with pathological changes in the posterior cerebral cortices and hippocampus were discussed.

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CitationGPTRetr11517

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: The fornix in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: The fornix is an integral white matter bundle located in the medial diencephalon and is part of the limbic structures. It serves a vital role in memory functions and as such has become the subject of recent research emphasis in Alzheimer's disease (AD) and mild cognitive impairment (MCI). As the characteristic pathological processes of AD progress, structural and functional changes to the medial temporal lobes and other regions become evident years before clinical symptoms are present. Though gray matter atrophy has been the most studied, degradation of white matter structures especially the fornix may precede these and has become detectable with use of diffusion tensor imaging (DTI) and other complimentary imaging techniques. Recent research utilizing DTI measurement of the fornix has shown good discriminability of diagnostic groups, particularly early and preclinical, as well as predictive power for incident MCI and AD. Stimulating and modulating fornix function by the way of DBS has been an exciting new area as pharmacological therapeutics has been slow to develop.

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CitationGPTRetr11518

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: Diffusion tensor imaging in Alzheimer's disease and mild cognitive impairment. Abstract of the paper: Structural magnetic resonance imaging (MRI) studies of Alzheimer's disease and mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal cortex; gray matter structures in the medial temporal lobe. Few studies have investigated the integrity of white matter in patients with AD or MCI. Diffusion tensor imaging (DTI) is a MRI technique that allows for the interrogation of the microstructural integrity of white matter. Based on increases in translational diffusion (mean diffusivity: MD) and decreases directional diffusion (fractional anisotropy: FA) damage to white matter can be assessed. Studies have identified regions of increased MD and decreased FA in patients with AD and MCI in all lobes of the brain, as well as medial temporal lobe structures including the hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in AD and MCI. Recent studies have exploited inter-voxel directional similarities to develop models of white matter pathways, and have used these models to assess the integrity of inter-cerebral connections. Particular focus has been applied to the parahippocampal white matter (including the perforant path) and the posterior cingulum. Although many studies have found DTI indicators of impaired white matter in AD and MCI, other studies have failed to detect any differences in MD or FA between the groups, demonstrating the need for large replicative studies. DTI is an evolving technique and advances in its application ought to provide new insights into AD and MCI.

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CitationGPTRetr11519

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: further analysis assessed areas where significant changes in fa and dr overlap termed fa dr from here on which is thought to highlight specific myelin damage Title of the paper: A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: We reviewed case-control studies of diffusion tensor imaging (DTI) in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI), in order to establish the relative severity and location of white matter microstructural changes. EMBASE and MEDLINE were searched using the keywords, (["diffusion tensor"] and ["Alzheimer*" or "mild cognitive impairment"]), as were reference lists of relevant papers. Forty-one diffusion tensor imaging studies contained data that were suitable for inclusion. Group means and standard deviations for fractional anisotropy and mean diffusivity, or p values from 2-sample tests, were extracted and pooled, using standard methods of meta-analysis and metaregression. Fractional anisotropy was decreased in AD in all regions except parietal white matter and internal capsule, while patients with MCI had lower values in all white matter regions except parietally and occipitally. Mean diffusivity was increased in AD in all regions, and in MCI in all but occipital and frontal regions.

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CitationGPTRetr11520

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Abstract of the paper: Magnetic resonance imaging (MRI) has been suggested as a useful tool in early diagnosis of Alzheimer's disease (AD). Based on MRI-derived volumes, we studied the hippocampus and entorhinal cortex (ERC) in 59 controls, 65 individuals with mild cognitive impairment (MCI) and 48 patients with AD. The controls and individuals with MCI were derived from population-based cohorts. Volumes of the hippocampus and ERC were significantly reduced in the following order: control > MCI > AD. Stepwise discriminant function analysis showed that the most efficient overall classification between controls and individuals with MCI subjects was achieved with ERC measurements (65.9%). However, the best overall classification between controls and AD patients (90.7%), and between individuals with MCI and AD patients (82.3%) was achieved with hippocampal volumes. Our results suggest that the ERC atrophy precedes hippocampal atrophy in AD. The ERC volume loss is dominant over the hippocampal volume loss in MCI, whereas more pronounced hippocampal volume loss appears in mild AD.

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CitationGPTRetr11521

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Abstract of the paper: OBJECTIVE To test the hypothesis that MRI-based measurements of hippocampal volume are related to the risk of future conversion to Alzheimer's disease (AD) in older patients with a mild cognitive impairment (MCI). BACKGROUND Patients who develop AD pass through a transitional state, which can be characterized as MCI. In some patients, however, MCI is a more benign condition, which may not progress to AD or may do so slowly. PATIENTS Eighty consecutive patients who met criteria for the diagnosis of MCI were recruited from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. METHODS At entry into the study, each patient received an MRI examination of the head, from which the volumes of both hippocampi were measured. Patients were followed longitudinally with approximately annual clinical/cognitive assessments. The primary endpoint was the crossover of individual MCI patients to the clinical diagnosis of AD during longitudinal clinical follow-up. RESULTS During the period of longitudinal observation, which averaged 32.6 months, 27 of the 80 MCI patients became demented. Hippocampal atrophy at baseline was associated with crossover from MCI to AD (relative risk [RR], 0.69, p = 0.015). When hippocampal volume was entered into bivariate models-using age, postmenopausal estrogen replacement, standard neuropsychological tests, apolipoprotein E (APOE) genotype, history of ischemic heart disease, and hypertension-the RRs were not substantially different from that found univariately, and the associations between hippocampal volume and crossover remained significant. CONCLUSION In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD.

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CitationGPTRetr11522

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Volume changes in Alzheimer's disease and mild cognitive impairment: cognitive associations. Abstract of the paper: OBJECTIVE To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects. MATERIAL AND METHODS In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period. RESULTS Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects. CONCLUSION Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers.

False

CitationGPTRetr11523

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Brain MRI hippocampal volume and prediction of clinical status in a mild cognitive impairment trial. Abstract of the paper: Mild Cognitive Impairment (MCI) is considered a transitional stage in the pathogenesis of Alzheimer's disease; however, not all MCI patients progress to clinically defined AD or decline at identical rates. Hippocampal atrophy, as measured by Magnetic Resonance Imaging (MRI), may be a marker for hippocampal pathology in patients with MCI and predict a more rapid deterioration to clinical AD. In this study, we used MRI data from an ongoing MCI clinical trial to determine whether MRI hippocampal volume at baseline was associated with cognitive and functional performance in MCI subjects and whether it predicted those individuals who were more likely to develop AD. We performed correlational analyses between the MRI hippocampal volumes at study entry and the subjects' concurrent performance on neuropsychological measures and clinical ratings. Larger hippocampal volume was associated with better performance on tests of memory, general cognition, and overall clinical ratings. Further analyses suggested that a smaller baseline hippocampal volume may be associated with a higher risk of developing clinical AD. As the trial is still ongoing, these results require confirmation once the trial is completed. In summary, these data suggest that MRI hippocampal volume may be a useful correlate of disease severity in MCI subjects and a prognostic indicator of subsequent AD.

False

CitationGPTRetr11524

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy. Abstract of the paper: Alzheimer's disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

False

CitationGPTRetr11525

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Volumes of the entorhinal and perirhinal cortices in Alzheimer's disease. Abstract of the paper: We measured the volumes of the entorhinal, perirhinal, and temporopolar cortices on magnetic resonance images by using a recently designed histology-based protocol in 30 patients with early Alzheimer's disease (AD) and 32 healthy control subjects. Compared to the controls, all of these cortical regions were significantly atrophied in AD patients (p < 0.0001). However, the entorhinal cortex was the most severely involved brain region studied, with 40% volume loss, and this region provided the highest discriminative accuracy (92%) in separating patients with AD from healthy control subjects. Importantly, the entorhinal volume loss was evident already in mild AD. In addition, the volume of the entorhinal cortex was not dependent on age, but it did correlate significantly with the severity of the disease. Because it assesses the major site of initial neuropathological changes in AD, magnetic resonance imaging volumetric measurement of the entorhinal cortex can offer a tool for distinguishing AD patients even in the very early stages of the disease from healthy aged subjects.

False

CitationGPTRetr11526

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Discriminating accuracy of medial temporal lobe volumetry and fMRI in mild cognitive impairment. Abstract of the paper: We investigated structural and functional changes in the medial temporal lobe (MTL) using magnetic resonance imaging (MRI) and compared the discriminative power of these measures with neuropsychological testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Functional MRI (fMRI) was performed in 21 elderly controls, 14 MCI subjects, and 15 mild AD patients during encoding and cued retrieval of word-picture pairs. A region-of-interest-based approach in SPM2 was used to extract the extent of hippocampal activation. The volumes of the hippocampus and entorhinal cortex (EC) were manually outlined from anatomical MR images. Discriminant analyses were conducted to assess the ability of hippocampal fMRI, MTL volumetry, and neuropsychological measures to classify subjects into clinical groups. Entorhinal but not hippocampal volumes differed significantly between the control and MCI subjects. Both entorhinal and hippocampal volumes differed between MCI and AD patients. There were no significant differences in the extent of hippocampal fMRI activation during encoding or retrieval between the groups. Entorhinal volume was the best discriminator with a discriminating accuracy of 85.7% between controls and MCI, 86.2% between MCI and AD, and 97.2% between controls and AD. Delayed recall of a wordlist classified the subjects, second best, with a discriminating accuracy of 81.8% between controls and MCI, 75% between MCI and AD and 93.5% between controls and AD. The accuracy of hippocampal volumetry ranged from 42.9 to 69.4%, and hippocampal fMRI activation during encoding and retrieval had a classification accuracy of only 41.4-57.7% between the groups. Our results suggest that evaluation of entorhinal atrophy, in addition to the prevailing diagnostic criteria, seems promising in the identification of prodromal AD. Future technical improvements may improve the utilization of hippocampal fMRI for early diagnostic purposes.

False

CitationGPTRetr11527

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Hippocampal atrophy rates in Alzheimer disease: added value over whole brain volume measures. Abstract of the paper: OBJECTIVE To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. METHODS We included 64 patients with AD (67 +/- 9 years; F/M 38/26), 44 patients with MCI (71 +/- 6 years; 21/23), and 34 controls (67 +/- 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 +/- 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. RESULTS All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5-22.2]), hippocampal atrophy rate (5.2 [1.9-14.3]), and whole brain atrophy rate (2.8 [1.1-7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1-606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. CONCLUSION Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD.

False

CitationGPTRetr11528

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: The role of volumetric MRI in understanding mild cognitive impairment and similar classifications. Abstract of the paper: We review nineteen empirical studies of mild cognitive impairment (MCI), age-associated memory impairment (AAMI) and related classifications reporting volumetric data on the hippocampus, entorhinal cortex and amygdala. Studies varied considerably in terms of the selection of participants, sample characteristics, the definitions of regions of interest and normalization techniques. Effect sizes for differences in left hippocampal volume and right hippocampal volumes of AAMI, MCI and pre-clinical dementia groups compared with controls ranged from 0.47 to 1.34. Effect sizes for left and right hippocampal volumes for Alzheimer's disease (AD) versus control were 1.88 and 1.75 respectively. Longitudinal results confirm that initial hippocampal volume is predictive of conversion to AD. Greater standardization in methodology and the development of normative age-referenced databases of regional brain volumes is required.

False

CitationGPTRetr11529

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD. Abstract of the paper: With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In the present study, 27 patients diagnosed with mild cognitive impairment (MCI) received a high-resolution MRI scan at baseline and were followed with yearly clinical evaluations. Ten of the 27 patients converted to AD during a 36-month period following the baseline clinical evaluation. Hippocampal and entorhinal cortex volumes derived from the baseline scan were compared to determine which of these two regions, known to be pathologically involved very early in the course of AD, could best differentiate MCI converters from non-converters. Although both entorhinal and hippocampal volumes were found to be independent predictors of the likelihood of conversion to AD, it was the right hemisphere entorhinal volume that best predicted conversion with a concordance rate of 93.5%.

True

CitationGPTRetr11530

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Abstract of the paper: OBJECTIVE MRI-based measurements of hippocampal atrophy are a sensitive indicator of the early pathologic degeneration of the medial temporal lobe in AD. However, AD pathology appears first in the transentorhinal/entorhinal cortex, not the hippocampus. The authors tested the hypothesis that MRI-based measurements of the entorhinal cortex are more sensitive than measurements of hippocampal volume in discriminating among three clinical groups; controls, patients with a mild cognitive impairment (MCI), and patients with mild probable AD. METHODS The authors studied 30 controls, 30 patients with MCI, and 30 patients with AD who were matched among clinical groups on age, gender, and education. All underwent a standardized MRI protocol from which the authors made measurements of hippocampal volume, entorhinal cortex volume, and the cumulative length of the medial border of the entorhinal cortex. RESULTS Pairwise intergroup differences (p < 0.01) were found for all MRI measurements with the exception of the cumulative length of the entorhinal cortex, which did not differentiate controls from MCI patients. Whereas the hippocampal and entorhinal cortex volume measurements provided slightly better intergroup discrimination than the entorhinal distance measurement, overall differences in discriminating ability among the three MRI measurements were minor. CONCLUSIONS Despite the theoretical rationale for the superiority of entorhinal measurements in early AD, the authors found MRI measurements of the hippocampus and entorhinal cortex were approximately equivalent at intergroup discrimination. Measurements of the hippocampus may be preferable because MRI depiction of the boundaries of the entorhinal cortex can be obscured by anatomic ambiguity, image artifact, or both.

False

CitationGPTRetr11531

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Abstract of the paper: The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

False

CitationGPTRetr11532

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Analysis of regional MRI volumes and thicknesses as predictors of conversion from mild cognitive impairment to Alzheimer's disease. Abstract of the paper: We determined predictors of conversion to Alzheimer's disease (AD) from mild cognitive impairment (MCI) with automated magnetic resonance imaging (MRI) regional cortical volume and thickness measures. One hundred amnestic MCI subjects, 118 AD patients, and 94 age-matched healthy controls were selected from AddNeuroMed study. Twenty-four regional cortical volumes and 34 cortical thicknesses were measured with automated image processing software at baseline. Twenty-one subjects converted from MCI to AD determined with the cognitive tests at baseline and 1 year later. The hippocampus, amygdala, and caudate volumes were significantly smaller in progressive MCI subjects than in controls and stable MCI subjects. The cortical volumes achieved higher predictive accuracy than did cognitive tests or cortical thickness. Combining the volumes, thicknesses, and cognitive tests did not improve the accuracy. The volume of amygdala and caudate were independent variables in predicting conversion from MCI to AD. We conclude that regional cortical volume measures are more powerful than those common cognitive tests we used in identifying AD patients at the very earliest stage of the disease.

False

CitationGPTRetr11533

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease. Abstract of the paper: BACKGROUND Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. METHODS We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm(3)/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects. RESULTS The age-corrected bilateral annualized atrophy rate (%/year) were: -1.6 (0.6) for CTRL, -2.2 (1.0) for MCI-nc, -3.2 (1.2) for MCI-co and -4.0 (1.5) for AD. Combined (v, Λ) discrimination ability gave an Area under the ROC curve (auc)=0.93 for CTRL vs AD and auc=0.88 for CTRL vs MCI-co. CONCLUSIONS Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information.

False

CitationGPTRetr11534

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: OBJECTIVES To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.

False

CitationGPTRetr11535

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI. Abstract of the paper: BACKGROUND Early pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer's disease (AD). OBJECTIVE To determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers. METHODS We studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1-weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space. RESULTS Volumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%. CONCLUSION Extent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.

False

CitationGPTRetr11536

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: MRI measures of entorhinal cortex vs hippocampus in preclinical AD. Abstract of the paper: BACKGROUND MRI measures of the entorhinal cortex and the hippocampus have been used to predict which nondemented individuals with memory problems will progress to meet criteria for AD on follow-up, but their relative accuracy remains controversial. OBJECTIVES To compare MRI measures of the entorhinal cortex and the hippocampus for predicting who will develop AD. METHODS MRI volumes of the entorhinal cortex and the hippocampus were obtained in 137 individuals comprising four groups: 1) individuals with normal cognition both at baseline and after 3 years of follow-up (n = 28), 2) subjects with memory difficulty but not dementia both at baseline and after 3 years of follow-up (n = 73), 3) subjects with memory difficulty at baseline who were diagnosed with probable AD within 3 years of follow-up (n = 21), and 4) patients with mild AD at baseline (n = 16). RESULTS Measures of both the entorhinal cortex and the hippocampus were different for each of the pairwise comparisons between the groups (p < 0.001) and were correlated with tests of memory (p < 0.01). However, the volume of the entorhinal cortex differentiated the subjects from those destined to develop dementia with considerable accuracy (84%), whereas the measure of the hippocampus did not. CONCLUSION These findings are consistent with neuropathologic data showing substantial involvement of the entorhinal cortex in the preclinical phase of AD and suggest that, as the disease spreads, atrophic change develops within the hippocampus, which is measurable on MRI.

False

CitationGPTRetr11537

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Rate of entorhinal and hippocampal atrophy in incipient and mild AD: relation to memory function. Abstract of the paper: In the present study, as part of a more extensive longitudinal investigation of the in vivo anatomical markers of early and incipient AD in our laboratory, three groups of elderly participants were followed with yearly clinical evaluations and high resolution MRI scans over a 6-year period (baseline and 5 years of follow-up). At baseline, participants consisted of: (1) 35 old subjects with no cognitive impairment (controls); (2) 33 participants with amnestic mild cognitive impairment (MCI); and (3) 14 patients with very mild AD. 11 participants with amnestic MCI received a diagnosis of AD over the follow-up period and 9 controls declined in cognitive function. T1 weighted MRI scans were acquired using a 3D SPGR pulse sequence. At baseline, both the amnestic MCI and mild AD groups differed from the controls in hippocampal and entorhinal cortex volume, but not from each other. Longitudinal analyses showed that the rate of atrophy of the entorhinal cortex and hippocampus for the stable controls differed significantly from MCI participants who converted to AD and the AD groups. Furthermore, longitudinal decreases in hippocampal and entorhinal volume were related to longitudinal decline in declarative memory performance. These findings suggest that the rate of atrophy of mesial temporal lobe structures can differentiate healthy from pathological aging.

False

CitationGPTRetr11538

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Functional implications of hippocampal volume and diffusivity in mild cognitive impairment. Abstract of the paper: Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early Alzheimer disease (AD), but the diagnostic significance of cross-sectionally determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI) in MCI patients revealed an association of microstructural changes in hippocampal areas with verbal memory decline. MRI volumetry and DTI were combined to investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and gender-matched healthy controls. Neuropsychological testing, high resolution T1-weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal areas were applied. Left hippocampal volume was significantly lower (-11%, P = 0.02) in MCI patients than in control subjects. No significant differences were found for the right hippocampus (-4%). Mean diffusivity (MD) was significantly elevated in MCI patients vs. controls in left (+10%, P = 0.002) and right hippocampal areas (+13%, P = 0.02). Hippocampal volume and MD values were not significantly correlated. Combining left hippocampal volume and MD measures showed that lower left hippocampal volumes were associated with poor verbal memory performance particularly when co-occurring with high MD values. No comparable associations could be found regarding the right hippocampal formation and with respect to non-verbal memory function. The results demonstrate that microstructural abnormalities as revealed by DTI are very sensitive early indicators of hippocampal dysfunction. The combination of macro- and microstructural parameters in hippocampal areas could be promising in early detection of neurodegenerative processes.

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CitationGPTRetr11539

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in addition to discriminating ad from controls volume measurements of the entorhinal cortex and hippocampus have been shown to discriminate mci patients who later progress to ad dementia from those who do not longitudinal studies have demonstrated that the rate of wholebrain atrophy increases more in earlyad patients than in controls in addition a recent study found that the rate of ventricular volume expansion predicted future mci in nondemented cohorts that were followed for up to 15 years and that this rate further accelerated years prior to the diagnosis of mci suggesting that this measurement is also useful as an antecedent biomarker Title of the paper: Measurement of precuneal and hippocampal volumes using magnetic resonance volumetry in Alzheimer's disease. Abstract of the paper: BACKGROUND AND PURPOSE Alzheimer's disease (AD) is associated with structural alterations in the medial temporal lobe (MTL) and functional alterations in the posterior cortical region, especially in the early stages. However, it is unclear what mechanisms underlie these regional discrepancies or whether the posterior cortical hypometabolism reflects disconnection from the MTL lesion or is the result of local pathology. The precuneus, an area of the posteromedial cortex that is involved in the early stages of AD, has recently received a great deal of attention in functional neuroimaging studies. To assess the relationship between the precuneus and hippocampus in AD, we investigated the volumes of these two areas using a magnetic resonance volumetric method. METHODS Twenty-three subjects with AD and 14 healthy age-matched controls underwent T1-weighted three-dimensional volumetric brain magnetic resonance imaging. Volumetric measurements were performed in the precuneus and hippocampus. RESULTS Compared to controls, AD patients exhibited a significant reduction in total precuneal volume, which was more prominent on the right side, and significant bilateral reductions in hippocampal volume. No correlation was found between the total volumes of the precuneus and hippocampus in the AD group. CONCLUSIONS These results suggest that volumetric measurements of both the precuneus and hippocampus are useful radiological indices for the diagnosis of AD. Furthermore, the lack of correlation is attributable to local pathology rather than being a secondary consequence of MTL pathology.

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CitationGPTRetr11540

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Intraneuronal Aβ accumulation, amyloid plaques, and synapse pathology in Alzheimer's disease. Abstract of the paper: BACKGROUND β-Amyloid (Aβ) plaques are a pathological hallmark of Alzheimer's disease (AD) and multiple lines of evidence have linked Aβ with AD. However, synapse loss is known as the best pathological correlate of cognitive impairment in AD, and intraneuronal Aβ accumulation has been shown to precede plaque pathology. The progression of Aβ accumulation to synapse loss and plaque formation remains incomplete. The objective is to investigate the progression of intraneuronal Aβ accumulation in the brain. METHODS To visualize and analyze the development of Aβ pathology we perform immunohistochemistry and immunofluorescence microscopy using antibodies against different Aβ conformations, synaptic proteins and structural neuronal proteins in brain tissue of AD transgenic mouse models. RESULTS Our results show the intraneuronal onset of Aβ42 accumulation in AD mouse brains with aging. We observe an inverse correlation of Aβ and amyloid fibrils with structural proteins within neurites. Images reveal aggregated amyloid within selective pyramidal neurons, neurites and synapses in AD transgenic mice as plaques arise. CONCLUSION The data support that Aβ42 accumulation and aggregation begin within AD-vulnerable neurons in the brain. Progressive intraneuronal Aβ42 aggregation disrupts the normal cytoarchitecture of neurites.

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CitationGPTRetr11541

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Synaptic degeneration in Alzheimer disease. Abstract of the paper: Alzheimer disease (AD) is characterized by progressive cognitive decline in older individuals accompanied by the presence of two pathological protein aggregates - amyloid-β and phosphorylated tau - in the brain. The disease results in brain atrophy caused by neuronal loss and synapse degeneration. Synaptic loss strongly correlates with cognitive decline in both humans and animal models of AD. Indeed, evidence suggests that soluble forms of amyloid-β and tau can cause synaptotoxicity and spread through neural circuits. These pathological changes are accompanied by an altered phenotype in the glial cells of the brain - one hypothesis is that glia excessively ingest synapses and modulate the trans-synaptic spread of pathology. To date, effective therapies for the treatment or prevention of AD are lacking, but understanding how synaptic degeneration occurs will be essential for the development of new interventions. Here, we highlight the mechanisms through which synapses degenerate in the AD brain, and discuss key questions that still need to be answered. We also cover the ways in which our understanding of the mechanisms of synaptic degeneration is leading to new therapeutic approaches for AD.

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CitationGPTRetr11542

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease. Abstract of the paper: BACKGROUND AND PURPOSE Synapse degeneration in Alzheimer's disease (AD) correlates strongly with cognitive decline. There is well-established excitatory synapse loss in AD with known contributions of pathological amyloid beta (Aβ) to excitatory synapse dysfunction and loss. Despite clear changes in circuit excitability in AD and model systems, relatively little is known about pathology in inhibitory synapses. METHODS Here human postmortem brain samples (n = 5 control, 10 AD cases) from temporal and occipital cortices were examined to investigate whether inhibitory synapses and neurons are lost in AD and whether Aβ may contribute to inhibitory synapse degeneration. Inhibitory neurons were counted in all six cortical layers using stereology software, and array tomography was used to examine synapse density and the accumulation of Aβ in synaptic terminals. RESULTS Differing inhibitory neuron densities were observed in the different cortical layers. The highest inhibitory neuron density was observed in layer 4 in both brain regions and the visual cortex had a higher inhibitory neuron density than the temporal cortex. There was significantly lower inhibitory neuron density in AD than in control cases in all six cortical layers. High-resolution array tomography imaging revealed plaque-associated loss of inhibitory synapses and accumulation of Aβ in a small subset of inhibitory presynaptic terminals with the most accumulation near amyloid plaques. CONCLUSIONS Inhibitory neuron and synapse loss in AD may contribute to disrupted excitatory/inhibitory balance and cognitive decline. Future work is warranted to determine whether targeting inhibitory synapse loss could be a useful therapeutic strategy.

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CitationGPTRetr11543

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Altered synaptic function in Alzheimer's disease. Abstract of the paper: Alzheimer's disease is the leading cause of dementia in the elderly, presenting itself clinically by progressive loss of memory and learning. Since synaptic density correlates more closely with cognitive impairment than any other pathological lesion observable in the disease pathology, an increased understanding of the mechanisms behind synaptic disconnection is of vital importance. Our lab investigated the neurotransmitter-specific status of distinct cortical presynaptic bouton populations in various transgenic mouse models of the Alzheimer's-like amyloid pathology in order to assess their involvement throughout the progression of the pathology. These studies have revealed that the amyloid pathology appears to progress in a neurotransmitter-specific manner where the cholinergic terminals appear most vulnerable, followed by the glutamatergic terminals and finally by the somewhat more resilient GABAergic terminals. This review will discuss additional studies which also provide evidence of a neurotransmitter-specific pathology as well as comment on the potential explanations for the observed vulnerabilities, touching upon metabolic demand, trophic support and receptor mediated activation.

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CitationGPTRetr11544

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits 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

CitationGPTRetr11545

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Synaptic loss in Alzheimer's disease and other dementias. Abstract of the paper: The extent and location of neuronal losses necessary or sufficient to produce dementia in patients with Alzheimer's Disease (AD) is unknown. To approach this question, we studied synaptic terminals in postmortem brain tissue utilizing immunohistochemical techniques. We used antibodies against two proteins found in synaptic terminals--synapsin I and synaptophysin--as synaptic markers in the hippocampal complexes of eight patients with autopsy-proven AD and eight nondemented control subjects. Quantitative microscopy measured the regional density of synaptic staining. All AD patients showed a striking decrease in synaptic staining in the outer half of the molecular layer of the dentate gyrus compared with control brains, where the density of synaptic terminals was uniform throughout. In an additional patient with progressive degenerative dementia but without plaques or tangles on neuropathologic examination, similar depletion of synaptic staining was seen in the dentate gyrus. Quantitative densitometric analyses confirmed the focal decrease in synaptic staining in the outer half of the molecular layer in demented patients. We also found a slight increase in synaptic staining in the inner half of this layer.

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CitationGPTRetr11546

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Synaptic degeneration in Alzheimer's disease. Abstract of the paper: Synaptic loss is the major neurobiological substrate of cognitive dysfunction in Alzheimer's disease (AD). Synaptic failure is an early event in the pathogenesis that is clearly detectable already in patients with mild cognitive impairment (MCI), a prodromal state of AD. It progresses during the course of AD and in most early stages involves mechanisms of compensation before reaching a stage of decompensated function. This dynamic process from an initially reversible functionally responsive stage of down-regulation of synaptic function to stages irreversibly associated with degeneration might be related to a disturbance of structural brain self-organization and involves morpho-regulatory molecules such as the amyloid precursor protein. Further, recent evidence suggests a role for diffusible oligomers of amyloid beta in synaptic dysfunction. To form synaptic connections and to continuously re-shape them in a process of ongoing structural adaptation, neurons must permanently withdraw from the cell cycle. Previously, we formulated the hypothesis that differentiated neurons after having withdrawn from the cell cycle are able to use molecular mechanisms primarily developed to control proliferation alternatively to control synaptic plasticity. The existence of these alternative effector pathways within neurons might put them at risk of erroneously converting signals derived from plastic synaptic changes into the program of cell cycle activation, which subsequently leads to cell death. The molecular mechanisms involved in cell cycle activation might, thus, link aberrant synaptic changes to cell death.

False

CitationGPTRetr11547

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Intracellular accumulation of amyloid-Beta - a predictor for synaptic dysfunction and neuron loss in Alzheimer's disease. Abstract of the paper: Despite of long-standing evidence that beta-amyloid (Abeta) peptides have detrimental effects on synaptic function, the relationship between Abeta, synaptic and neuron loss is largely unclear. During the last years there is growing evidence that early intraneuronal accumulation of Abeta peptides is one of the key events leading to synaptic and neuronal dysfunction. Many studies have been carried out using transgenic mouse models of Alzheimer's disease (AD) which have been proven to be valuable model systems in modern AD research. The present review discusses the impact of intraneuronal Abeta accumulation on synaptic impairment and neuron loss and provides an overview of currently available AD mouse models showing these pathological alterations.

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CitationGPTRetr11548

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits 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.

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CitationGPTRetr11549

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: The Role of Glial Cells and Synapse Loss in Mouse Models of Alzheimer's Disease. Abstract of the paper: Synapse loss has detrimental effects on cellular communication, leading to network disruptions within the central nervous system (CNS) such as in Alzheimer's disease (AD). AD is characterized by a progressive decline of memory function, cognition, neuronal and synapse loss. The two main neuropathological hallmarks are amyloid-β (Aβ) plaques and neurofibrillary tangles. In the brain of AD patients and in mouse models of AD several morphological and functional changes, such as microgliosis and astrogliosis around Aβ plaques, as well as dendritic and synaptic alterations, are associated with these lesions. In this review article, we will summarize the current literature on synapse loss in mouse models of AD and discuss current and prospective treatments for AD.

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CitationGPTRetr11550

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Spines, plasticity, and cognition in Alzheimer's model mice. Abstract of the paper: The pathological hallmarks of Alzheimer's disease (AD)--widespread synaptic and neuronal loss and the pathological accumulation of amyloid-beta peptide (Aβ) in senile plaques, as well as hyperphosphorylated tau in neurofibrillary tangles--have been known for many decades, but the links between AD pathology and dementia and effective therapeutic strategies remain elusive. Transgenic mice have been developed based on rare familial forms of AD and frontotemporal dementia, allowing investigators to test in detail the structural, functional, and behavioral consequences of AD-associated pathology. Here, we review work on transgenic AD models that investigate the degeneration of dendritic spine structure, synaptic function, and cognition. Together, these data support a model of AD pathogenesis in which soluble Aβ initiates synaptic dysfunction and loss, as well as pathological changes in tau, which contribute to both synaptic and neuronal loss. These changes in synapse structure and function as well as frank synapse and neuronal loss contribute to the neural system dysfunction which causes cognitive deficits. Understanding the underpinnings of dementia in AD will be essential to develop and evaluate therapeutic approaches for this widespread and devastating disease.

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CitationGPTRetr11551

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: The inside-out amyloid hypothesis and synapse pathology in Alzheimer's disease. Abstract of the paper: Cumulative evidence in brains and cultured neurons of Alzheimer's disease (AD) transgenic mouse models, as well as in human postmortem AD brains, highlights that age-related increases in β-amyloid peptide (Aβ), particularly in endosomes near synapses, are involved in early synapse dysfunction. Our immunoelectron microscopy and high-resolution immunofluorescence microscopy studies show that this early subcellular Aβ accumulation leads to progressive Aβ aggregation and pathology, particularly within dystrophic neurites and synapses. These studies confirm that neuritic/synaptic Aβ accumulation is the nidus of plaque formation. Aβ-dependent synapse pathology in AD models is modulated by synaptic activity and is plaque independent. The amyloid precursor protein (APP) is normally transported down neurites and appears to be preferentially processed to Aβ at synapses. Synapses are sites of early Aβ accumulation and aberrant tau phosphorylation in AD, which alter the synaptic composition at early stages of the disease. Elucidating the normal role of APP, and potentially of Aβ, at synapses should provide important insights into the mechanism(s) of Aβ-induced synapse dysfunction in AD and how to therapeutically mitigate these dysfunctions.

False

CitationGPTRetr11552

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Mechanisms of synaptic dysfunction in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is characterized by a progressive cognitive decline in which memory, initiation, learning and conceptualization are severely affected. The main histopathological alterations are the presence of amyloid beta/A4-containing plaques, tangles and amyloid angiopathy. It is believed that these brain alterations are associated with abnormal expression and/or processing of amyloid precursor protein (APP) and with abnormal assembly of cytoskeletal proteins. Recent quantitative studies with the electron microscope and with immunochemical/immunocytochemical assays, using molecular markers for synaptic proteins, have shown that synaptic loss in the cortex is the major correlate of the patterns of cognitive decline in AD. The synaptic loss in AD is accompanied by neuronal loss and aberrant sprouting, and studies in incipient AD cases have shown that this alteration occurs very early in the progression of the disease preceding tangle formation and neuronal loss. These results suggest that damage to the synaptic terminal plays a central role in the pathogenesis of AD. The mechanisms of synaptic pathology in AD are not yet clear, however, studies in transgenic animal models support the possibility that APP participates in synaptic stabilization and that abnormal metabolism of this molecule could lead to synaptic dysfunction which, in turn, results in neurodegeneration and dementia.

False

CitationGPTRetr11553

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Abstract of the paper: The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer's disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer's disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer's disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer's disease, and what we know from Alzheimer's disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer's disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer's disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer's disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer's disease. The synapse will certainly continue to be an important target within Alzheimer's disease for the foreseeable future.

False

CitationGPTRetr11554

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice. Abstract of the paper: Accumulation of β-amyloid (Aβ) and loss of synapses are hallmarks of Alzheimer's disease (AD). How synaptic activity relates to Aβ accumulation and loss of synapses is a current topic of major interest. Synaptic activation promotes Aβ secretion, and chronic reduction of synaptic activity reduced Aβ plaques in an AD transgenic mouse model. This suggested beneficial effects of reducing synaptic activity in AD. We now show that reduced synaptic activity causes detrimental effects on synapses and memory despite reducing plaques using two different models of chronic synaptic inhibition: deafferentation of the barrel cortex and administration of benzodiazepine. An interval of prolonged synaptic inhibition exacerbated loss of synaptophysin compared with synaptically more active brain in AD transgenic but not wild-type mice. Furthermore, an interval of benzodiazepine treatment, followed by a washout period, exacerbated memory impairment in AD transgenic mice. Exacerbation of synaptic and behavioral abnormalities occurred in the setting of reduced Aβ plaques but elevated intraneuronal Aβ immunoreactivity. These data support beneficial effects of synaptic activation on Aβ-related synaptic and behavioral impairment in AD.

False

CitationGPTRetr11555

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice. Abstract of the paper: Major pathological findings in Alzheimer's disease (AD) brain include the deposition of amyloid-beta and synapse loss. Synaptic loss has been shown to correlate with the cognitive decline in AD patients, but the relationship between cerebral amyloidosis and synapse loss is complicated by the presence of neurofibrillary tangles and other lesions in AD brain. With the use of the APP23 transgenic mouse model that overexpresses human amyloid precursor protein (APP) with the Swedish double mutation, we investigated whether the development of cortical amyloid deposition was accompanied by synaptic bouton loss. With stereological methods, we show that despite robust age-related cortical amyloid deposition with associated synaptic degeneration, the total number of cortical synaptophysin-positive presynaptic terminals is not changed in 24-month-old animals compared with 3-, 8-, and 15-month-old APP23 mice. Wild-type mice also do not show an age-related loss of presynaptic boutons in the neocortex and are not significantly different from APP23 mice. Synaptophysin Western blotting revealed no significant difference between APP23 mice and wild-type controls at 3 and 25 months of age. Our results suggest that cerebral amyloidosis is not sufficient to account for the global synapse loss in AD. Alternatively, a putative trophic effect of APP may prevent, compensate, or delay a loss of synapses in this mouse model.

False

CitationGPTRetr11556

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Spread of tau down neural circuits precedes synapse and neuronal loss in the rTgTauEC mouse model of early Alzheimer's disease. Abstract of the paper: Synaptic dysfunction and loss is the strongest pathological correlate of cognitive decline in Alzheimer's disease (AD) with increasing evidence implicating neuropathological tau protein in this process. Despite the knowledge that tau spreads through defined synaptic circuits, it is currently unknown whether synapse loss occurs before the accumulation of tau or as a consequence. To address this, we have used array tomography to examine an rTgTauEC mouse model expressing a P301L human tau transgene and a transgene labeling cytoplasm red (tdTomato) and presynaptic terminals green (Synaptophysin-EGFP). All transgenes are restricted primarily to the entorhinal cortex using the neuropsin promotor to drive tTA expression. It has previously been shown that rTgTauEC mice exhibit neuronal loss in the entorhinal cortex and synapse density loss in the middle molecular layer (MML) of the dentate gyrus at 24 months of age. Here, we observed the density of tau-expressing and total presynapses, and the spread of tau into the postsynapse in the MML of 3-6, 9, and 18 month old red-green-rTgTauEC mice. We observe no loss of synapse density in the MML up to 18 months even in axons expressing tau. Despite the maintenance of synapse density, we see spread of human tau from presynaptic terminals to postsynaptic compartments in the MML at very early ages, indicating that the spread of tau through neural circuits is not due to the degeneration of axon terminals and is an early feature of the disease process.

False

CitationGPTRetr11557

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease. Abstract of the paper: Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss.

False

CitationGPTRetr11558

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Synapse loss and progress of Alzheimer's disease -A network model. Abstract of the paper: We present observational evidence from studies on primary cortical cultures from AD transgenic mice, APPSwe/PS1ΔE9 (APP/PS1) mice, for significant decrease in total spine density at DIV-15 and onward. This indicates reduction in potential healthy synapses and strength of connections among neurons. Based on this, a network model of neurons is developed, that explains the consequent loss of coordinated activity and transmission efficiency among neurons that manifests over time. The critical time when structural connectivity in the brain undergoes a phase-transition, from initial robustness to irreparable breakdown, is estimated from this model. We also show how the global efficiency of signal transmission in the network decreases over time. Moreover, the number of multiple paths of high efficiency decreases rapidly as the disease progresses, indicating loss of structural plasticity and inefficiency in choosing alternate paths or desired paths for any pattern of activity. Thus loss of spines caused by β-Amyloid (Aβ) peptide results in disintegration of the neuronal network over time with consequent cognitive dysfunctions in Alzheimer's Disease (AD).

False

CitationGPTRetr11559

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: loss of neuronal synaptic density and synapse number represents another invariant feature of ad that appears to precede overt neuronal degeneration notably it has been shown that the loss of synaptic terminals correlates better with cognitive decline than plaque and tangle load or neuronal loss leading to the concept that losing synapses is one of the key events leading to cognitive dysfunction in ad there is accumulating evidence from ad transgenic mice that intraneuronal aβ142 triggers not only early neuronal loss but also synaptic deficits Title of the paper: Intraneuronal amyloid beta and reduced brain volume in a novel APP T714I mouse model for Alzheimer's disease. Abstract of the paper: Transgenic mouse models of Alzheimer's disease (AD) expressing high levels of amyloid precursor protein (APP) with familial AD (FAD) mutations have proven to be extremely useful in understanding pathogenic processes of AD especially those that involve amyloidogenesis. We earlier described Austrian APP T714I pathology that leads to one of the earliest AD age-at-onsets with abundant intracellular and extracellular amyloid deposits in brain. The latter strikingly was non-fibrillar diffuse amyloid, composed of N-truncated A beta 42 in absence of A beta 40. In vitro, this mutation leads to one of the highest A beta 42/A beta 40 ratios among all FAD mutations. We generated an APP T714I transgenic mouse model that despite having 10 times lower transgene than endogenous murine APP deposited intraneuronal A beta in brain by 6 months of age. Accumulations increased with age, and this was paralleled by decreased brain sizes on volumetric MRI, compared to age-matched and similar transgene-expressing APP wild-type mice, although, with these levels of transgenic expression we did not detect neuronal loss or significant memory impairment. Immunohistochemical studies revealed that the majority of the intraneuronal A beta deposits colocalized with late endosomal markers, although some A beta inclusions were also positive for lysosomal and Golgi markers. These data support earlier observations of A beta accumulation in the endosomal-lysosomal pathway and the hypothesis that intraneuronal accumulation of A beta could be an important factor in the AD pathogenesis.

False

CitationGPTRetr11560

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Genetics of Alzheimer's disease. Abstract of the paper: Mutations in any one of three genes can cause autosomal dominant, early-onset Alzheimer's disease: these genes are the amyloid precursor protein (APP) gene on chromosome 21, the presenilin-1 (PS-1) gene on chromosome 14 and the presenilin-2 (PS-2) gene on chromosome 1. Pathogenic mutations at all these loci cause mismetabolism of APP such that more of the peptide A beta 42 is produced. This peptide is deposited in the plaques in the brains of Alzheimer's patients. These facts have led to the dominant hypothesis for the disease process: the 'amyloid cascade hypothesis', which proposes that overproduction or failure to clear the peptide A beta 42 is always central to the disease. Genetic variability at the apoliprotein E locus is a major determinant of late onset Alzheimer's disease. The mechanism by which apoliprotein E is involved in the pathogenesis of Alzheimer's disease is not yet known. There are likely to be other genetic factors which impinge on Alzheimer's disease.

False

CitationGPTRetr11561

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Identification of PSEN1 and APP gene mutations in Korean patients with early-onset Alzheimer's disease. Abstract of the paper: Although mutations in three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), have been identified as genetic causes of early-onset Alzheimer s disease (EOAD), there has been a single report on a PSEN1 mutation in Koreans. In the present study, we performed a genetic analysis of six Korean patients with EOAD. Direct sequencing analysis of the APP, PSEN1 and PSEN2 genes revealed two different mutations of the PSEN1 gene (G206S and M233T) and one mutation of the APP gene (V715M) in three patients with age-at-onset of 34, 35, and 42 yr, respectively. In addition, two patients with age-at-onset of 55 and 62 yr, respectively, were homozygous for APOE epsilon 4 allele. One woman had no genetic alterations. These findings suggest that PSEN1 and APP gene mutations may not be uncommon in Korean patients with EOAD and that genetic analysis should be provided to EOAD patients not only for the identification of their genetic causes but also for the appropriate genetic counseling.

False

CitationGPTRetr11562

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Presymptomatic Genetic Testing with an APP Mutation in Early-Onset Alzheimer Disease: A Descriptive Study of Sibship Dynamics. Abstract of the paper: Early-onset Alzheimer disease (AD) accounts for only 5% of all cases of Alzheimer disease. To date, mutations in three different genes, the Amyloid precursor protein (APP), Presenilin 1 (PS1), and Presenilin 2 (PS2), have been identified as causative in early-onset AD, making predictive testing possible. Predictive testing for early-onset Alzheimer disease is a relatively new phenomenon. This paper describes the process of identifying a new mutation in the APP gene associated with early-onset AD, notifying family members, and offering participation in research as well as predictive testing. The goal is to share the complexities of predictive testing in a sibship newly identified as being at risk for an adult-onset, incurable neurodegenerative disease.

False

CitationGPTRetr11563

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: The genetics of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a genetically complex disorder. Mutations in the amyloid precursor protein and presenilin 1 (PS1) genes are fully penetrant and cause early-onset AD. Mutations in presenilin 2, a PS1 homologue, cause partially penetrant autosomal dominant AD with onset age beginning at 40 years and extending past 75 years. A fourth gene, apolipoprotein E (ApoE) is a risk-factor for late-onset AD. Over 40 genes have been tested as AD candidate genes, yet none has been clearly established as an AD risk factor. Linkage studies have implicated a number of chromosome regions as possible sites for late-onset AD loci with the strongest evidence being for chromosome 12. Candidate genes in this region include alpha2-macroglobulin (A2M) and low-density lipoprotein receptor-related gene (LRP), although neither has been clearly established as an AD gene. Identification of additional late-onset genes will require larger samples, more sophisticated analysis methods, and large-scale positional cloning efforts.

False

CitationGPTRetr11564

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation. Abstract of the paper: A subset of early-onset Alzheimer's disease is inherited as an autosomal-dominant trait and is associated with mutations in the genes encoding β-amyloid precursor protein, presenilin 1, or presenilin 2. In this study, we identified 2 PSEN1 mutations (1 novel and 1 known) in 2 unrelated Iranian families with autosomal-dominant Alzheimer's disease. The disease progressed rapidly with a mean age at onset of 33 and 42 years and an age at death ranging from 43 to 48 years.

False

CitationGPTRetr11565

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations. Abstract of the paper: Mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) are major genetic causes of early-onset Alzheimer's disease (EOAD). Clinical heterogeneity is frequently observed in patients with PSEN1 and PSEN2 mutations. Using whole exome sequencing, we screened a Dutch cohort of 68 patients with EOAD for rare variants in Mendelian Alzheimer's disease, frontotemporal dementia, and prion disease genes. We identified 3 PSEN1 and 2 PSEN2 variants. Three variants, 1 in PSEN1 (p.H21Profs*2) and both PSEN2 (p.A415S and p.M174I), were novel and absent in control exomes. These novel variants can be classified as probable pathogenic, except for PSEN1 (p.H21Profs*2) in which the pathogenicity is uncertain. The initial clinical symptoms between mutation carriers varied from behavioral problems to memory impairment. Our findings extend the mutation spectrum of EOAD and underline the clinical heterogeneity among PSEN1 and PSEN2 mutation carriers. Screening for Alzheimer's disease-causing genes is indicated in presenile dementia with an overlapping clinical diagnosis.

False

CitationGPTRetr11566

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Abstract of the paper: Mutations in the presenilin genes (PS-1 and PS-2) cause early onset autosomal dominant Alzheimer's disease (AD). Eight early-onset, autopsy-documented familial AD kindreds were screened for mutations in PS-1, and seven different mutations were identified. Three of these were new mutations (G209V, A426P, and E120D), two were previously reported mutations in new families, and three mutations were confirmed in previously published families. Two of these new mutations are found within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is the most C-terminal PS-1 mutation identified to date.

False

CitationGPTRetr11567

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Abstract of the paper: Mutations in three causative genes have been identified in patients with an autosomal-dominant form of early-onset Alzheimer's disease (EOAD). To determine the spectrum of mutations in a group consisting of 40 Polish patients with clinically diagnosed familial EOAD and 1 patient with mild cognitive impairment (MCI) and family history of AD, we performed a screening for mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) genes. Four previously recognized pathogenic mutations in PSEN1 gene (H163R, M139V) and APP gene (T714A, V715A), and three novel putative mutations in PSEN1 gene (P117R and I213F) and PSEN2 gene (Q228L) were identified. The 34 patients with no mutations detected were older than the patients with mutations. A frequency of APOE4 allele was higher in this group. Frequency of mutations is relatively low (17%), possibly due to used operational definition of a patient with familial EOAD (a patient having at least one relative with early-onset dementia). It could be concluded that screening for mutations in the three genes could be included in a diagnostic program directed at patients with a positive family history or age of onset before 55 years.

False

CitationGPTRetr11568

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Two Novel Mutations and a de novo Mutation in PSEN1 in Early-onset Alzheimer's Disease. Abstract of the paper: Presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) mutations are responsible for autosomal dominant early-onset Alzheimer's disease (AD-EOAD). To analyze the phenotypes and genotypes of EOAD patients, we performed comprehensive clinical assessments as well as mutation screening of PSEN1, PSEN2, and exons 16 and 17 of APP by Sanger sequencing in the three Chinese EOAD families. We identified two novel mutations of PSEN1 (Y256N and H214R) in samples from these families, and a de novo mutation of PSEN1 (G206V) in a patient with very early-onset sporadic Alzheimer's disease. A combination of bioinformatics tools based on evolutionary, structural and computational methods predicted that the mutations were all deleterious. These findings suggest that PSEN1 Y256N, H214R, and G206V need to be considered as potential causative mutations in EOAD patients. Further functional studies are needed to evaluate the roles of these mutations in the pathogenesis of AD.

False

CitationGPTRetr11569

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Presenilin 1 gene mutation (M139I) in a patient with an early-onset Alzheimer's disease: clinical characteristics and genetic identification. Abstract of the paper: Mutations in the presenilin 1 (PSEN1) gene are more commonly identified as genetic causes of early-onset familial Alzheimer's disease than mutations in the amyloid precursor protein (APP) and the presenilin 2 (PSEN2) genes. More than 100 different mutations in the PSEN1 gene have been detected, and the clinical phenotypes have been described in the literature. This paper reports the case of a 38-year-old female showing early memory impairment and having a base pair mutation from guanine (G) to cytosine (C) at codon 139 of PSEN1, which leads to the substitution of a methionine with an isoleucine.

False

CitationGPTRetr11570

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: New insights into the genetics of Alzheimer's disease. Abstract of the paper: In early 1993, the genetic data implicating the amyloid precursor protein as one of the loci leading to early onset Alzheimer's disease were reviewed (Hardy and Duff, Annals of Medicine, 25: 437-440), together with the evidence implicating abnormal deposition of beta-amyloid as the initiating point of the process leading to the disease. Since that time, three other genetic loci have been directly implicated in the aetiology of the disease: the apolipoprotein E locus on chromosome 19, the presenilin 1 gene on chromosome 14 and the presenilin 2 gene on chromosome 1. In this article, I review the progress over the last three years and attempt to assess whether the evidence for the amyloid cascade hypothesis still stands scrutiny.

False

CitationGPTRetr11571

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Novel mutations and repeated findings of mutations in familial Alzheimer disease. Abstract of the paper: Twenty-one unrelated patients with a history of suspected familial Alzheimer disease (FAD) were screened for mutations in PSEN1, PSEN2, and APP, the known FAD genes encoding the presenilins (PS1 and PS2) and the amyloid precursor protein (APP). The mutation detection rate was 57%. Of the nine pathogenic mutations found in 12 cases, three were in APP, one in PSEN2, and five in PSEN1, including two novel Greek mutations (L113Q and N135S). Whereas our findings suggest the possibility of single founders for the majority of mutations, we found evidence of recurrence of the APP mutations V717L and V717I.

False

CitationGPTRetr11572

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Genetic dissection of Alzheimer disease, a heterogeneous disorder. Abstract of the paper: The genetics of Alzheimer disease (AD) are complex and not completely understood. Mutations in the amyloid precursor protein gene (APP) can cause early-onset autosomal dominant AD. In vitro studies indicate that cells expressing mutant APPs overproduce pathogenic forms of the A beta peptide, the major component of AD amyloid. However, mutations in the APP gene are responsible for 5% or less of all early-onset familial AD. A locus on chromosome 14 is responsible for AD in other early-onset AD families and represents the most severe form of the disease in terms of age of onset and rate of decline. Attempts to identify the AD3 gene by positional cloning methods are underway. At least one additional early-onset AD locus remains to be located. In late-onset AD, the apolipoprotein E gene allele epsilon 4 is a risk factor for AD. This allele appears to act as a dose-dependent age-of-onset modifier. The epsilon 2 allele of this gene may be protective. Other late-onset susceptibility factors remain to be identified.

False

CitationGPTRetr11573

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Unraveling the genes implicated in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder and it is the most common form of dementia in the elderly. Early onset AD is caused by mutations in three genes: Amyloid-β precursor protein, presenilin 1 (PSEN1) and PSEN2. Late onset AD (LOAD) is complex and apolipoprotein E is the only unanimously accepted genetic risk factor for its development. Various genes implicated in AD have been identified using advanced genetic technologies, however, there are many additional genes that remain unidentified. The present review highlights the genetics of early and LOAD and summarizes the genes involved in different signaling pathways. This may provide insight into neurodegenerative disease research and will facilitate the development of effective strategies to combat AD.

False

CitationGPTRetr11574

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: A locus for familial early-onset Alzheimer's disease on the long arm of chromosome 14, proximal to the alpha 1-antichymotrypsin gene. Abstract of the paper: Although mutations in the beta-amyloid precursor protein gene (APP) on chromosome 21 cause some cases of early-onset Alzheimer's disease (AD), most cases evidently do not have mutations in APP. We analysed ten early-onset families for linkage to APP and markers elsewhere in the genome. One family (F172) was consistent with linkage to chromosome 21 and was subsequently found to have an APP Val to Ile mutation. Of the others, all but one were consistent with linkage to markers in the middle long arm of chromosome 14. However, no family showed independent evidence of linkage with two point analysis and only one showed independent evidence of linkage on multipoint analysis. Therefore, we cannot rule out heterogeneity at these loci although tests for heterogeneity were not significant.

False

CitationGPTRetr11575

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene. Abstract of the paper: CONTEXT Alzheimer disease is the most common form of dementia. Mutations in the genes amyloid precursor protein (APP), presenilin 1(PS1) and presenilin 2(PS2) have been found in early-onset familial forms of Alzheimer disease OBJECTIVE To determine the cause of dementia in a family with early-onset illness. DESIGN, SETTING, AND PARTICIPANTS A family with a history of dementia was referred to the Indiana Alzheimer Disease Center, Indianapolis. All the research in this study was done in a university or university hospital. The proband and her 4 siblings took part in the study. The proband, who is still alive, showed symptoms of Alzheimer disease at 38 years of age. Genomic DNA was obtained from blood samples of 5 family members. The APPandPS1genes of the proband were screened for mutations by amplification followed by direct sequencing. RESULTS Sequence of exon 17 of the APPgene revealed a single nucleotide (guanine to cytosine) substitution in 1 allele, resulting in an amino acid change at codon 717 (valine to leucine). Each of the proband's siblings were tested for this mutation by direct sequencing. Two of the 4 were found to have the mutation; one of whom was recently clinically diagnosed at the age of 36 years. CONCLUSIONS A novel mutation in the APPgene (V717L) has been found in a family with a history of dementia, beginning in the mid to late 30s. The age of onset in this family is earlier than most of the other families with Alzheimer disease who also have APPmutations. Arch Neurol. 2000.

False

CitationGPTRetr11576

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. Abstract of the paper: We analyzed 12 families with autosomal dominant early-onset Alzheimer' s disease (EOAD)for mutations in the coding region of the presenilin I (PSNLI) gene corresponding to the AD3 locus on chromosome 14q24.3. A total of eight missense mutations at codons 82, 115, 139, 163, 231, 264, 392, and 410 including six novel mutations, were identified in eight families. Cosegregation of the mutations with EOAD was confirmed in three families, one including 36 affected individuals. This study underlines the great allelic heterogeneity and the large distribution of the mutations within the PSNLI coding region. Our results support the notion that PSNLI is the major gene involved in autosomal dominant EOAD.

False

CitationGPTRetr11577

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Novel PSEN1 G209A mutation in early-onset Alzheimer dementia supported by structural prediction. Abstract of the paper: BACKGROUND Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. CASE REPORT A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. CONCLUSION We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.

False

CitationGPTRetr11578

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

False

CitationGPTRetr11579

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: multiplex earlyonset alzheimers disease eoad pedigrees facilitated the identification of mutations in three genes the amyloid precursor protein app presenilin 1 psen1 and presenilin 2 psen2 Title of the paper: The solved and unsolved mysteries of the genetics of early-onset Alzheimer's disease. Abstract of the paper: Approximately half of the Alzheimer's disease (AD) cases that are associated with early onset appear to be transmitted as a pure genetic, autosomal dominant trait. Genetic analyses of these pedigrees have found three causal genes: betaAPP, presenilin 1 (PS1), and presenilin 2 (PS2). This review provides an update on the pathological consequences of mutations in early-onset AD genes, the phenotypic heterogeneity of those cases, and future directions for research and clinical practice.

False

CitationGPTRetr11580

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. Abstract of the paper: Docosahexaenoic acid (DHA), the main omega-3 fatty acid, is concentrated and avidly retained in membrane phospholipids of the nervous system. DHA is involved in brain and retina function, aging, and neurological and psychiatric/behavioral illnesses. Neuroprotectin D1 (NPD1), the first-identified stereoselective bioactive product of DHA, exerts neuroprotection in models of experimental stroke by down-regulating brain ischemia reperfusion (BIR)-induced leukocyte infiltration, proinflammatory signaling, and infarct size. Moreover, NPD1 inhibits cytokine-mediated cyclooxygenase-2 (COX-2) expression. Photoreceptor membranes display the highest content of DHA of any cell. Retinal pigment epithelial cells participate in the phagocytosis of the tips of photoreceptor cells (photoreceptor outer segment renewal). There is a DHA retrieval-intercellular mechanism between both types of cells that conserves this fatty acid during this process. NPD1 promotes homeostatic regulation of the integrity of these two cells, particularly during oxidative stress, and this protective signaling may be relevant in retinal degenerative diseases. Moreover, neurotrophins are NPD1-synthesis agonists, and NPD1 content is decreased in the CA1 region of the hippocampus of Alzheimer's patients. Overall, NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42 production and its neurotoxicity. Thus, NPD1 elicits potent cell-protective, anti-inflammatory, prosurvival repair signaling.

False

CitationGPTRetr11581

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. Abstract of the paper: Deficiency in docosahexaenoic acid (DHA), a brain-essential omega-3 fatty acid, is associated with cognitive decline. Here we report that, in cytokine-stressed human neural cells, DHA attenuates amyloid-beta (Abeta) secretion, an effect accompanied by the formation of NPD1, a novel, DHA-derived 10,17S-docosatriene. DHA and NPD1 were reduced in Alzheimer disease (AD) hippocampal cornu ammonis region 1, but not in the thalamus or occipital lobes from the same brains. The expression of key enzymes in NPD1 biosynthesis, cytosolic phospholipase A2 and 15-lipoxygenase, was altered in AD hippocampus. NPD1 repressed Abeta42-triggered activation of proinflammatory genes while upregulating the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1). Soluble amyloid precursor protein-alpha stimulated NPD1 biosynthesis from DHA. These results indicate that NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42-induced neurotoxicity.

True

CitationGPTRetr11582

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Docosahexaenoic acid and the aging brain. Abstract of the paper: The dietary essential PUFA docosahexaenoic acid [DHA; 22:6(n-3)] is a critical contributor to cell structure and function in the nervous system, and deficits in DHA abundance are associated with cognitive decline during aging and in neurodegenerative disease. Recent studies underscore the importance of DHA-derived neuroprotectin D1 (NPD1) in the homeostatic regulation of brain cell survival and repair involving neurotrophic, antiapoptotic and antiinflammatory signaling. Emerging evidence suggests that NPD1 synthesis is activated by growth factors and neurotrophins. Evolving research indicates that NPD1 has important determinant and regulatory interactions with the molecular-genetic mechanisms affecting beta-amyloid precursor protein (betaAPP) and amyloid beta (Abeta) peptide neurobiology. Deficits in DHA or its peroxidation appear to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in Alzheimer disease (AD), a common and progressive age-related neurological disorder unique to structures and processes of the human brain. This article briefly reviews our current understanding of the interactions of DHA and NPD1 on betaAPP processing and Abeta peptide signaling and how this contributes to oxidative and pathogenic processes characteristic of aging and AD pathology.

False

CitationGPTRetr11583

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Abstract of the paper: The biosynthesis of oxygenated arachidonic acid messengers triggered by cerebral ischemia-reperfusion is preceded by an early and rapid phospholipase A2 activation reflected in free arachidonic and docosahexaenoic acid (DHA) accumulation. These fatty acids are released from membrane phospholipids. Both fatty acids are derived from dietary essential fatty acids; however, only DHA, the omega-3 polyunsaturated fatty acyl chain, is concentrated in phospholipids of various cells of brain and retina. Synaptic membranes and photoreceptors share the highest content of DHA of all cell membranes. DHA is involved in memory formation, excitable membrane function, photoreceptor cell biogenesis and function, and neuronal signaling, and has been implicated in neuroprotection. In addition, this fatty acid is required for retinal pigment epithelium cell (RPE) functional integrity. Here we provide an overview of the recent elucidation of a specific mediator generated from DHA that contributes at least in part to its biological significance. In oxidative stress-challenged human RPE cells and rat brain undergoing ischemia-reperfusion, 10,17S-docosatriene (neuroprotectin D1, NPD1) synthesis evolves. In addition, calcium ionophore A23187, IL-1beta, or the supply of DHA enhances NPD1 synthesis. A time-dependent release of endogenous free DHA followed by NPD1 formation occurs, suggesting that a phospholipase A2 releases the mediator's precursor. When NPD1 is infused during ischemia-reperfusion or added to RPE cells during oxidative stress, apoptotic DNA damage is down-regulated. NPD1 also up-regulates the anti-apoptotic Bcl-2 proteins Bcl-2 and BclxL and decreases pro-apoptotic Bax and Bad expression. Moreover, NPD1 inhibits oxidative stress-induced caspase-3 activation. NPD1 also inhibits IL-1beta-stimulated expression of COX-2. Overall, NPD1 protects cells from oxidative stress-induced apoptosis. Because photoreceptors are progressively impaired after RPE cell damage in retinal degenerative diseases, understanding of how these signals contribute to retinal cell survival may lead to the development of new therapeutic strategies. Moreover, NPD1 bioactivity demonstrates that DHA is not only a target of lipid peroxidation, but rather is the precursor to a neuroprotective signaling response to ischemia-reperfusion, thus opening newer avenues of therapeutic exploration in stroke, neurotrauma, spinal cord injury, and neurodegenerative diseases, such as Alzheimer disease, aiming to up-regulate this novel cell-survival signaling.

False

CitationGPTRetr11584

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Lipid-mediated cell signaling protects against injury and neurodegeneration. Abstract of the paper: Deficiency in docosahexaenoic acid (DHA) is associated with impaired visual and neurological development, cognitive decline, macular degeneration, and other neurodegenerative diseases. DHA is concentrated in phospholipids of the brain and retina, with photoreceptor cells having the highest DHA content of all cell membranes. The discovery that neuroprotectin D1 (NPD1; 10R, 17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) is a bioactive mediator of DHA sheds light on the biological importance of this fatty acid. In oxidative stress-challenged human retinal pigment epithelial (RPE) cells, human brain cells, or brain ischemia-reperfusion, NPD1 synthesis is enhanced as a response for sustaining homeostasis. Thus, neurotrophins, Abeta peptide (Abeta)42, calcium ionophore A23187, interleukin-1beta (IL-1beta), or DHA supply enhances NPD1 synthesis. NPD1, in turn, upregulates the antiapoptotic proteins of the Bcl-2 family and decreases the expression of proapoptotic Bcl-2 family members. In human neural cells, DHA attenuates Abeta42 secretion, resulting in concomitant formation of NPD1. NPD1 repressed Abeta42-triggered activation of proinflammatory genes and upregulated the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1) in human brain cells in culture. Overall, NPD1 signaling regulates brain and retinal cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42-induced neurotoxicity and other forms of cell injury. These in turn support homeostasis during brain and retinal aging, counteract inflammatory signaling, and downregulate events that support the initiation and progression of neurodegenerative disease.

False

CitationGPTRetr11585

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Docosahexaenoic acid and its derivative neuroprotectin D1 display neuroprotective properties in the retina, brain and central nervous system. Abstract of the paper: The significance of the selective enrichment in omega-3 essential fatty acids (docosahexaenoyl - DHA - chains of membrane phospholipids, 22C and 6 double bonds) in the nervous system (e.g. synaptic membranes and dendrites) has remained, until recently, incompletely understood. While studying mechanisms of neuronal survival, we contributed to the discovery of a docosanoid synthesized by 15-lipoxygenase-1 from DHA, which we dubbed neuroprotectin D1 (NPD1;10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15E,19Z hexaenoic acid). NPD1 is a docosanoid because it is derived from a 22C precursor (DHA), unlike eicosanoids, which are derived from the 20C arachidonic acid family of essential fatty acids not enriched in the nervous system. We found that NPD1 is promptly made in response to oxidative stress, seizures and brain ischemia-reperfusion. NPD1 is neuroprotective in experimental brain damage, retinal pigment epithelial cells, and in human brain cells. Thus, NPD1 acts as a protective sentinel, one of the very first defenses activated when cell homeostasis is threatened by neurodegenerations. NPD1 also has been shown to have a specificity and potency that provides beneficial bioactivity during initiation and early progression of neuronal and retinal degenerations, epilepsy and stroke. In short, NPD1 regulation promotes homeostatic regulation of neural circuitry integrity.

False

CitationGPTRetr11586

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer's disease models. Abstract of the paper: Neuroprotectin D1 (NPD1) is a stereoselective mediator derived from the omega-3 essential fatty acid docosahexaenoic acid (DHA) with potent inflammatory resolving and neuroprotective bioactivity. NPD1 reduces Aβ42 peptide release from aging human brain cells and is severely depleted in Alzheimer's disease (AD) brain. Here we further characterize the mechanism of NPD1's neurogenic actions using 3xTg-AD mouse models and human neuronal-glial (HNG) cells in primary culture, either challenged with Aβ42 oligomeric peptide, or transfected with beta amyloid precursor protein (βAPP)(sw) (Swedish double mutation APP695(sw), K595N-M596L). We also show that NPD1 downregulates Aβ42-triggered expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) and of B-94 (a TNF-α-inducible pro-inflammatory element) and apoptosis in HNG cells. Moreover, NPD1 suppresses Aβ42 peptide shedding by down-regulating β-secretase-1 (BACE1) while activating the α-secretase ADAM10 and up-regulating sAPPα, thus shifting the cleavage of βAPP holoenzyme from an amyloidogenic into the non-amyloidogenic pathway. Use of the thiazolidinedione peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone, the irreversible PPARγ antagonist GW9662, and overexpressing PPARγ suggests that the NPD1-mediated down-regulation of BACE1 and Aβ42 peptide release is PPARγ-dependent. In conclusion, NPD1 bioactivity potently down regulates inflammatory signaling, amyloidogenic APP cleavage and apoptosis, underscoring the potential of this lipid mediator to rescue human brain cells in early stages of neurodegenerations.

False

CitationGPTRetr11587

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection. Abstract of the paper: Deficiency in docosahexaenoic acid (DHA) is associated with impaired visual and neurological postnatal development, cognitive decline, macular degeneration, and other neurodegenerative diseases. DHA is an omega-3 polyunsaturated fatty acyl chain concentrated in phospholipids of brain and retina, with photoreceptor cells displaying the highest content of DHA of all cell membranes. The identification and characterization of neuroprotectin D1 (NPD1, 10R, 17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) contributes in understanding the biological significance of DHA. In oxidative stress-challenged human retinal pigment epithelial (RPE) cells, human brain cells, or rat brains undergoing ischemia-reperfusion, NPD1 synthesis is enhanced as a response for sustaining homeostasis. Thus, neurotrophins, Abeta peptide 42 (Abeta42), calcium ionophore A23187, interleukin (IL)-1beta, or DHA supply enhances NPD1 synthesis. NPD1, in turn, up-regulates the antiapoptotic proteins of the Bcl-2 family and decreases the expression of proapoptotic Bcl-2 family members. Moreover, NPD1 inhibits IL-1beta-stimulated expression of cyclooxygenase-2 (COX-2). Because both RPE and photoreceptors are damaged and then die in retinal degenerations, elucidating how NPD1 signaling contributes to retinal cell survival may lead to a new understanding of disease mechanisms. In human neural cells, DHA attenuates amyloid-beta (Abeta) secretion, resulting in concomitant formation of NPD1. NPD1 was found to be reduced in the Alzheimer's disease (AD) cornu ammonis region 1 (CA1) hippocampal region, but not in other areas of the brain. The expression of key enzymes for NPD1 biosynthesis, cytosolic phospholipase A(2) (cPLA(2)), and 15-lipoxygenase (15-LOX) was found altered in the AD hippocampal CA1 region. NPD1 repressed Abeta42-triggered activation of pro-inflammatory genes and upregulated the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1) in human brain cells in culture. Overall, these results support the concept that NPD1 promotes brain and retina cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42-induced neurotoxicity and other forms of cell injury, which in turn fosters homeostasis during development in aging, as well as during the initiation and progression of neurodegenerative diseases.

False

CitationGPTRetr11588

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection. Abstract of the paper: Docosahexaenoic acid, enriched in the brain and retina, generates docosanoids in response to disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimer's disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-κB subtype that, in turn, enhances expression of BIRC3 (baculoviral inhibitor of apoptosis repeat-containing protein 3) in the retina and in experimental stroke, leading to neuroprotection. Elucidating the mechanisms of action of docosanoids will contribute to managing diseases, including stroke, AD, age-related macular degeneration, traumatic brain injury, Parkinson's disease, and other neurodegenerations.

False

CitationGPTRetr11589

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Abstract of the paper: PURPOSE OF REVIEW To summarize recent findings that docosahexaenoate (DHA) is the precursor of stereospecific derivatives with anti-inflammatory and cytoprotective properties. RECENT FINDINGS The docosahexaenoate-derived mediator neuroprotectin D1 is formed in retinal pigment epithelial cells when confronted with oxidative stress, in the brain during experimental stroke, and in the human brain from Alzheimer's disease patients as well as in human brain cells in culture. Neuroprotectin D1 displays potent anti-inflammatory and neuroprotective bioactivity. SUMMARY Here, we summarize recent studies demonstrating that in brain ischemia-reperfusion and in retinal pigment epithelial cells exposed to oxidative stress stereospecific docosahexaenoate-oxygenation pathways are activated and lead to the formation of docosanoid messengers. Two docosahexaenoate-oxygenation pathways were identified: the first is responsible for the formation of the messenger neuroprotectin D1 and the second pathway, which is active in the presence of aspirin, leads to the formation of the resolvin-type mediators (17R-DHA). Neuroprotectin D1 induces antiapoptotic, anti-inflammatory signaling and is neuroprotective.

False

CitationGPTRetr11590

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Abstract of the paper: Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to retinal pigment epithelium (RPE) and retina. Photoreceptor and synaptic membranes share the highest content of DHA of all cell membranes. This fatty acid is required for RPE functional integrity; however, it is not known whether specific mediators generated from DHA contribute to its biological significance. We used human ARPE-19 cells and demonstrated the synthesis of 10,17S-docosatriene [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore A-23187, by IL-1beta, or by supplying DHA. Under these conditions, there is a time-dependent release of endogenous free DHA followed by NPD1 formation, suggesting that phospholipase A(2) releases the mediator's precursor. Added NPD1 potently counteracted H(2)O(2)/tumor necrosis factor alpha oxidative-stress-triggered apoptotic RPE DNA damage. NPD1 also up-regulated the antiapoptotic proteins Bcl-2 and Bcl-x(L) and decreased proapoptotic Bax and Bad expression. Moreover, NPD1 (50 nM) inhibited oxidative-stress-induced caspase-3 activation. NPD1 also inhibited IL-1beta-stimulated expression of cyclooxygenase 2 promoter transfected into ARPE-19 cells. Overall, NPD1 protected RPE cells from oxidative-stress-induced apoptosis, and we predict that it will similarly protect neurons. This lipid mediator therefore may indirectly contribute to photoreceptor cell survival as well. Because both RPE and photoreceptor cells die in retinal degenerations, our findings contribute to the understanding of retinal cell survival signaling and potentially to the development of new therapeutic strategies.

True

CitationGPTRetr11591

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Survival signalling in Alzheimer's disease. Abstract of the paper: Significant advancements in our understanding of cell-survival signalling in AD (Alzheimer's disease) stem from recent investigations into the metabolism, trafficking and fate of the essential omega-3 fatty acid DHA (docosahexaenoic acid) (C(22:6), n=3). Brain synaptic terminals and neuronal plasma membranes are highly enriched in DHA, and deficiencies in this polyunsaturated fatty acid are characteristic of AD-affected brain. Oxidative stress, targeting phospholipids containing DHA, and age-related DHA depletion are associated with the progressive erosion of normal cognitive function in AD. Current studies support the idea that DHA itself and novel DHA-derived neural synapse- and membrane-derived lipid messengers have considerable potential to modulate cell survival signalling in stressed cultured neural cell models in vitro and in mammalian models of learning, memory and AD in vivo. Key players in this intrinsic rescue system include the alpha-secretase-processed neurotrophin sAPPalpha [soluble APPalpha (amyloid precursor protein alpha)] peptide, the DHA-derived 10,17S-docosatriene NPD1 (neuroprotectin D1), a tandem brain cytosolic phospholipase A(2) and 15-lipoxygenase enzymatic system that biosynthesizes NPD1, and a small family of anti-apoptotic neuroprotective genes that encode Bcl-2, Bcl-X(L) and Bfl-1 (A1). This paper reviews current ideas regarding DHA and the oxygenated DHA derivative NPD1, intrinsically triggered biolipid neuroprotectants that along with their associated rescue pathways, contribute to life-or-death decisions of brain cells during homoeostasis, aging and neurodegenerative disease.

False

CitationGPTRetr11592

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: The docosanoid neuroprotectin D1 induces homeostatic regulation of neuroinflammation and cell survival. Abstract of the paper: The onset of neurodegenerations and nervous system injury both trigger cell signaling perturbations that lead to damage of neuronal circuits and synapic connections, as well as protective signaling that aims to halt disease onset. Here we review recent findings that support the role of the docosanoid mediator neuroprotectin D1 (NPD1) as an early response or sentinel during the initial phase of nervous system damage. NPD1 is derived from docosahexaenoic acid that is selectively concentrated and retained in the nervous system. The protein misfolding triggers the biosynthesis of NPD1 which in turn downregulates pathways that lead to cell death and changes the outcome to cell survival. Proteotoxic stress as a result of protein misfolding is a widespread event in many neurodegenerative diseases. Therefore, mechanisms and mediators such as NPD1 that curtail consequences of these events are of interest as leads in the search for novel preventive and or therapeutic approaches.

False

CitationGPTRetr11593

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Neuroprotectin D1 induces neuronal survival and downregulation of amyloidogenic processing in Alzheimer's disease cellular models. Abstract of the paper: The mediator neuroprotectin D1 (NPD1) is an enzymatic derivative of the omega-3 essential fatty acid docosahexaenoic acid. NPD1 stereoselectively and specifically binds to human retinal pigment epithelium (RPE) cells and neutrophils. In turn, this lipid mediator induces dephosphorylation of Bcl-x(L) in a PP2A-dependent manner and induces PI3K/Akt and mTOR/p70S6K pathways leading to RPE cell survival during oxidative stress-induced apoptosis. As a proof of principle of its systemic in vivo bioactivity, NPD1 attenuates laser-induced choroidal neovascularization in mice. Using human neural cells transfected with amyloid precursor protein (APP)sw (Swedish double mutation APP695sw, K595N, M596L), NPD1 was shown to regulate secretase-mediated production of Aβ peptide, downregulates pro-inflammatory gene expression, and promotes cell survival. In human neural cells overexpressing beta-amyloid precursor protein (βAPP), the lipid mediator suppressed Aβ42 shedding by downregulating β-secretase (BACE1) while activating the α-secretase (ADAM10), thus shifting the βAPP cleavage from the noxious amyloidogenic pathway into a non-amyloidogenic, neurotrophic pathway. Furthermore, downregulation of Aβ42 peptide release by NPD1 may be dependent upon PPARγ activation. In conclusion, NPD1 exhibits anti-inflammatory, anti-amyloidogenic, and anti-apoptotic bioactivities in human neural cells in part via PPARγ signaling and through the targeting of α- and β-secretase systems.

False

CitationGPTRetr11594

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging--impact of Bcl-2 and NPD-1 like metabolites. Abstract of the paper: The present study investigated the effects of orally administered long chain omega-3 polyunsaturated fatty acids (PUFA) on mitochondrial function and processing of the amyloid precursor protein (APP) in brains of young (3 months old) and aged (24 months old) NMRI-mice. Neuroprotective properties of fish oil (FO) (1.6 ml/kg p.o.) were assessed ex vivo after 21 days in dissociated brain cells (DBC) and isolated mitochondria. Docosahexaenoic acid (DHA) levels were significantly lower in blood and brains of aged mice which were compensated by FO administration. Isolated DBC and mitochondria from aged mice showed significantly lower adenosine triphosphate (ATP) levels and reduced activity of complexes I+II and IV of the mitochondrial respiration system, respectively. FO restored the age-related decrease in respiration and improved ATP production. Moreover, FO increased the levels of anti-apoptotic Bcl-2 protein. Cell membrane fractions isolated from the brain of aged mice exhibited lower membrane fluidity, which was partially improved under FO treatment. In comparison to young animals, levels of neuroprotective sAPPα were significantly lower in the brain of aged mice. However, levels of sAPPα, Aβ and C-terminal APP fragments (CTF) were largely unchanged after FO treatment in aged mice. Neuroprotectin D-1 (NPD-1) represents a neuroprotective compound that is derived from unesterified DHA. Levels of NPD1-like metabolites (NPD1-like) and of unesterified DHA were significantly increased in brains of aged mice. FO treatment further strongly increased NPD1-like levels indicating an accelerated conversion rate of free DHA to NPD1-like. Our findings provide new mechanisms underlying the neuroprotective actions of omega-3 PUFA and identified FO as a promising nutraceutical to delay age-related mitochondrial dysfunction in the brain.

False

CitationGPTRetr11595

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases. Abstract of the paper: Essential polyunsaturated fatty acids (PUFAs) are critical nutritional lipids that must be obtained from the diet to sustain homeostasis. Omega-3 and -6 PUFAs are key components of biomembranes and play important roles in cell integrity, development, maintenance, and function. The essential omega-3 fatty acid family member docosahexaenoic acid (DHA) is avidly retained and uniquely concentrated in the nervous system, particularly in photoreceptors and synaptic membranes. DHA plays a key role in vision, neuroprotection, successful aging, memory, and other functions. In addition, DHA displays anti-inflammatory and inflammatory resolving properties in contrast to the proinflammatory actions of several members of the omega-6 PUFAs family. This review discusses DHA signalolipidomics, comprising the cellular/tissue organization of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains rich in DHA-containing phospholipids, and the cellular and molecular events revealed by the uncovering of signaling pathways regulated by DHA and docosanoids, the DHA-derived bioactive lipids, which include neuroprotectin D1 (NPD1), a novel DHA-derived stereoselective mediator. NPD1 synthesis agonists include neurotrophins and oxidative stress; NPD1 elicits potent anti-inflammatory actions and prohomeostatic bioactivity, is anti-angiogenic, promotes corneal nerve regeneration, and induces cell survival. In the context of DHA signalolipidomics, this review highlights aging and the evolving studies on the significance of DHA in Alzheimer's disease, macular degeneration, Parkinson's disease, and other brain disorders. DHA signalolipidomics in the nervous system offers emerging targets for pharmaceutical intervention and clinical translation.

False

CitationGPTRetr11596

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors. Abstract of the paper: Recent data have provided important clues about the molecular mechanisms underlying certain retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration. Photoreceptor cell degeneration is a feature common to these diseases, and the death of these cells in many instances seems to involve the closely associated retinal pigment epithelial (RPE) cells. Under normal circumstances, both cell types are subject to potentially damaging stimuli (e.g. sunlight and high oxygen tension). However, the mechanism or mechanisms by which homeostasis is maintained in this part of the eye, which is crucial for sight, are an unsolved riddle. The omega-3 fatty acid family member docosahexaenoic acid (DHA), which is enriched in these cells, is the precursor of neuroprotectin D1 (NPD1). NPD1 inhibits oxidative-stress-mediated proinflammatory gene induction and apoptosis, and consequently promotes RPE cell survival. This enhanced understanding of the molecular basis of endogenous anti-inflammatory and neuroprotective signaling in the RPE presents an opportunity for the development of therapies for retinal degenerative diseases.

False

CitationGPTRetr11597

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: NPD1 induction of retinal pigment epithelial cell survival involves PI3K/Akt phosphorylation signaling. Abstract of the paper: Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes survival in cells exposed to oxidative stress by inducing the activity of anti-inflammatory mediators and suppressing the expression of pro-inflammatory genes. Though retinal pigment epithelial (RPE) cells naturally produce NPD1 from DHA, investigating the mechanisms through which exogenous NPD1 induces cell survival is essential to assess mechanisms of actions and the potential of this lipid mediator for treatment of retinal degenerative diseases. The PI3K/Akt and mTOR/p70S6K pathways are responsible for supporting cell survival upon exposure to oxidative stress. In human ARPE-19 cells pretreated with NPD1 then exposed to varying concentrations of oxidative stress or repeated exposures to oxidative stress, Akt, mTOR, and p70S6K were phosphorylated to a greater extent and for a greater duration than cells not pretreated with NPD1. In addition to increased phosphorylation, a subsequent decreased rate of apoptosis was observed upon NPD1 treatment. Thus NPD1 bioactivity in RPE cells enhances activation of these pathways and promotes cell integrity and survival.

False

CitationGPTRetr11598

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Omega-3 Polyunsaturated Fatty Acids and Oxylipins in Neuroinflammation and Management of Alzheimer Disease. Abstract of the paper: Alzheimer disease (AD) is becoming one of the most prevalent neurodegenerative conditions worldwide. Although the disease progression is becoming better understood, current medical interventions can only ameliorate some of the symptoms but cannot slow disease progression. Neuroinflammation plays an important role in the advancement of this disorder, and n-3 (ω-3) polyunsaturated fatty acids (PUFAs) are involved in both the reduction in and resolution of inflammation. These effects may be mediated by the anti-inflammatory and proresolving effects of bioactive lipid mediators (oxylipins) derived from n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in fish oil. Although interventions have generally used fish oil containing both EPA and DHA, several studies that used either EPA or DHA alone or specific oxylipins derived from these fatty acids indicate that they have distinct effects. Both DHA and EPA can reduce neuroinflammation and cognitive decline, but EPA positively influences mood disorders, whereas DHA maintains normal brain structure. Fewer studies with a plant-derived n-3 PUFA, α-linolenic acid, suggest that other n-3 PUFAs and their oxylipins also may positively affect AD. Further research identifying the unique anti-inflammatory and proresolving properties of oxylipins from individual n-3 PUFAs will enable the discovery of novel disease-management strategies in AD.

False

CitationGPTRetr11599

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the 15lipoxygenase1 15lox1 dhaderived npd1 displays neuroprotective bioactivity in brain and retinal cells against various insults including oxidative injury ischemiareperfusion and inflammation Title of the paper: Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Abstract of the paper: Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer's disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.

False