APOE ε4 allele drives female-specific Alzheimer's disease progression via vascular dysfunction and tau spreading.

ABSTRACT:

Background

Apolipoprotein E (APOE) epsilon4 (ε4) is a major genetic risk factor for late-onset Alzheimer's disease (AD), with women exhibiting heightened vulnerability to APOE ε4-associated cognitive impairment. Despite recognition of this sexual dimorphism, the underlying biological mechanisms remain incompletely understood.

Methods

We performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data from the Mayo Clinic cohort (n = 277 temporal cortex samples) to identify sex- and APOE ε4-linked co-expression modules. 315 hub genes were identified within the most relevant gene modules derived from female AD patients with APOE ε4. The expression patterns of representative hub genes were then validated in female APOE ε4 carriers. Causal genes were priorit

SUBMITTER: Huang S 

PROVIDER: S-EPMC12705627 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature