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- W2898202497 abstract "The pattern and progression of neurofibrillary tangle (NFT) pathology in Alzheimer's Disease (AD) is well-characterized by Braak staging. However, a subset of AD cases deviates from typical staging. Murray et al suggested in 2011 that two neuropathologically distinct atypical subtypes exist: hippocampal sparing AD (HpSp) and limbic predominant AD (LP) – each having characteristic sets of clinical attributes distinct from typical AD. We hypothesize that the variable limbic and cortical distribution of NFTs underlying these subtypes may reflect differences in the exposures of neural networks to AD pathology and explain atypical clinical heterogeneity. We assessed NFT density throughout selected cortical and limbic sections in a clinicopathological cohort (n=70) of AD cases enriched for atypical clinical presentations. We classified cases as typical, HpSp, or LP using an algorithm based on cortical and limbic NFT density. Main cognitive domains (executive, visuospatial, language, and memory function) were assessed using an established composite z score. A Mann-Whitney U-Test was used to analyze differences of regional NFT density between subgroups, and multivariate linear regression was used to evaluate relationships between regional NFT density and clinical characteristics. Clinical and demographic information for this sample are depicted in table 1. The limbic NFT density accounts for just 21.2% of the variance in the cortical NFT density, correcting for age and sex. Limbic NFT density is significantly higher in female patients (p=0.004), and higher burden is significantly associated with longer disease duration (p = 0.010) and more severe memory symptoms (p=0.008). Cortical, but not limbic, NFT density is inversely correlated with age of death (p<0.001). Cortical NFT density is significantly higher in females (p=0.007) and in cases with an atypical clinical diagnosis (p=0.013). A higher cortical burden is associated with more severe language symptoms (p=0.015). The distinct clinical correlates of limbic and cortical NFT densities and the low variance of cortical NFT density accounted for by limbic NFT density suggests differential regional vulnerabilities to tau pathology. Understanding the pathological basis for clinical heterogeneity in AD presents an opportunity to hone mechanistic therapies for different clinical manifestations." @default.
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- W2898202497 date "2018-07-01" @default.
- W2898202497 modified "2023-10-16" @default.
- W2898202497 title "P1‐494: REGIONAL NEUROFIBRILLARY TANGLE DISTRIBUTION AS A CONTRIBUTOR TO CLINICAL HETEROGENEITY IN ALZHEIMER'S DISEASE" @default.
- W2898202497 doi "https://doi.org/10.1016/j.jalz.2018.06.504" @default.
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