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Female-specific risk of Alzheimer's disease is associated with tau phosphorylation processes: A transcriptome-wide interaction analysis.

Abstract：

:The levels of tau phosphorylation differ between sexes in Alzheimer's disease (AD). Transcriptome-wide associations of sex by disease interaction could indicate whether specific genes underlie sex differences in tau pathology; however, no such study has been reported yet. We report the first analysis of the effect of the interaction between disease status and sex on differential gene expression, meta-analyzing transcriptomic data from the 3 largest publicly available case-control studies (N = 785) in the brain to date. A total of 128 genes, significantly associated with sex-AD interactions, were enriched in phosphoproteins (false discovery rate (FDR) = 0.001). High and consistent associations were found for the overexpressions of NCL (FDR = 0.002), whose phosphorylated protein generates an epitope against neurofibrillary tangles and KIF2A (FDR = 0.005), a microtubule-associated motor protein gene. Transcriptome-wide interaction analyses suggest sex-modulated tau phosphorylation, at sites like Thr231, Ser199, or Ser202 that could increase the risk of women to AD and indicate sex-specific strategies for intervention and prevention.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Cáceres A,González JR

doi

10.1016/j.neurobiolaging.2020.08.020

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

104-108

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(20)30276-1

journal_volume

96

pub_type

杂志文章

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