CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex-specific alteration of multiple proteins involved in Alzheimer's disease.

ABSTRACT:

Introduction

In Alzheimer's disease (AD), females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited.

Methods

We comprehensively examined 6162 proteins in cerebrospinal fluid (CSF) from 2496 participants to identify sex-specific proteomic alteration by CSF amyloid beta (Aβ)42 and phosphorylated tau (p-tau) levels.

Results

We identified and replicated 68 male-specific and 116 female-specific proteins associated with Aβ42 and/or p-tau levels. Apolipoprotein E ε4 carrier status modified sex-specific alterations of multiple proteins including S100A9 and NEFL for Aβ42 and MAPK9 and MAPKAPK2 for p-tau. Male-specific proteins, enriched in microglia, were involved in activating innate immune response. The male network exhibite

SUBMITTER: Do AN 

PROVIDER: S-EPMC12782156 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature