Proteomic subtyping of Alzheimer's disease CSF links blood-brain barrier dysfunction to reduced levels of tau and synaptic biomarkers.

ABSTRACT:

Introduction

Alzheimer's disease (AD) shows clinical and molecular heterogeneity shaped by demographic and genetic factors.

Methods

To resolve this heterogeneity, we performed a network-based proteomic analysis of cerebrospinal fluid (CSF) from 431 individuals, including 111 African Americans, to identify protein co-expression modules and define AD subtypes.

Results

Ten co-expression modules reflecting diverse pathways and cell types were identified, many linked to demographics and AD biomarkers. One subtype, enriched in African Americans and males, showed low CSF tau, elevated plasma proteins, and reduced synaptic proteins, features consistent with blood-brain barrier (BBB) dysfunction. This subtype also showed the highest levels of thrombin activity, capable of clea

SUBMITTER: Bangs MC 

PROVIDER: S-EPMC12580855 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature