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Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study.

Abstract：

:Many elderly individuals remain dementia-free throughout their life. However, some of these individuals exhibit Alzheimer disease neuropathology on autopsy, evidenced by neurofibrillary tangles (NFTs) in AD-specific brain regions. We conducted a genome-wide association study to identify genetic mechanisms that distinguish non-demented elderly with a heavy NFT burden from those with a low NFT burden. The study included 299 non-demented subjects with autopsy (185 subjects with low and 114 with high NFT levels). Both a genotype test, using logistic regression, and an allele test provided consistent evidence that variants in the RELN gene are associated with neuropathology in the context of cognitive health. Immunohistochemical data for reelin expression in AD-related brain regions added support for these findings. Reelin signaling pathways modulate phosphorylation of tau, the major component of NFTs, either directly or through β-amyloid pathways that influence tau phosphorylation. Our findings suggest that up-regulation of reelin may be a compensatory response to tau-related or beta-amyloid stress associated with AD even prior to the onset of dementia.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Kramer PL,Xu H,Woltjer RL,Westaway SK,Clark D,Erten-Lyons D,Kaye JA,Welsh-Bohmer KA,Troncoso JC,Markesbery WR,Petersen RC,Turner RS,Kukull WA,Bennett DA,Galasko D,Morris JC,Ott J

doi

10.1016/j.neurobiolaging.2010.01.010

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

2113-22

issue

12

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(10)00040-0

journal_volume

32

pub_type

杂志文章

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