Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.

ABSTRACT:

Introduction

Sex differences exist in Alzheimer's disease (AD), but the underlying mechanisms remain unclear.

Methods

We examined brain proteomes profiled from the dorsolateral prefrontal cortex of 770 donors (66.2% female).

Results

Proteome-wide differential expression analysis in males and females jointly identified many significant proteins for AD dementia (n = 1228), amyloid beta (n = 1183), tangles (n = 1309), and global cognitive trajectory (n = 2325) at a false discovery rate of <0.05. Sex-stratified analyses also identified many proteins associated with AD or its endophenotypes. Finally, we found 10 proteins with significant sex-by-trait interactions, including one in AD clinical diagnosis (MARCKS), seven in cognitive trajectories (TOGARAM1, PLCD3, SLC22A5, MT

SUBMITTER: Mei Z 

PROVIDER: S-EPMC12064417 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature