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Background: Selective corticolimbic vulnerability to tau pathology in Alzheimer's disease (AD) underlies clinicopathologic heterogeneity. The goal of this presentation will be to examine spatial heterogeneity of tangle distribution on a continuum through the utility of the corticolimbic index (CLix).
Method: We will discuss the development of CLix in the Florida Autopsied Multi-Ethnic (FLAME) cohort, which sought to collapse the spatial distribution of thioflavin-S tangle counts in AD (n=1361) to assign a continuum: hippocampal sparing with cortical predominance (<10), representative/typical (≥10 to <30), and limbic predominant with cortical sparing (≥30).
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Alzheimers Dement
December 2024
cheonan chungmu hospital, cheonan si, Korea, Republic of (South).
Background: Vascular contributions to dementia & Alzheimer's disease are increasing recognized. Recent studies have suggested that blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction, including the early clinical stages of AD. Apolipoprotein E4(APOE4), the major AD susceptibility gene, leads to accelerated blood-brain barrier breakdown & degeneration of brain capillary pericyte that maintain blood-brain barrier integrity.
View Article and Find Full Text PDFDeveloping Topics.
Alzheimers Dement
December 2024
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing, China.
Background: Microglia play a critical role in the pathogenesis and development of Alzheimer's disease (AD). Selective small-molecule colony-stimulating factor 1 receptors (CSF1R) inhibitor, designed to deplete microglia, could be used to meliorate AD. This study aimed to investigate the effects and mechanisms of chimeric antigen receptor T (CAR-T) cells targeting CSF1R in 6-month-old APP/PS1 male mice.
View Article and Find Full Text PDFBackground: Oxylipins are oxygenated fatty acid (FA) metabolites that are important mediators of inflammation. Neuroinflammation is a hallmark of Alzheimer's disease (AD), and brains of AD patients contain more pro-inflammatory and less anti-inflammatory oxylipins compared to healthy controls. Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor for medium and long-chain FAs, including, but not limited to, omega-3-polyunsaturated FAs.
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Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: SHIP1 is a phosphatidyl inositol phosphatase encoded by INPP5D, which has been identified as a risk gene for Alzheimer's disease (AD). SHIP1 is expressed in microglia, the resident macrophage in brain. It is a complex, multidomain protein that acts as a negative regulator downstream from TREM2.
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