Proteomic Subtyping of Alzheimer's Disease CSF links Blood-Brain Barrier Dysfunction to Reduced levels of Tau and Synaptic Biomarkers.

ABSTRACT: Alzheimer's disease (AD) is characterized by significant clinical and molecular heterogeneity, influenced by genetic and demographic factors. Using an unbiased, network-driven approach, we analyzed the cerebrospinal fluid (CSF) proteome from 431 individuals (483 samples), including 111 African American participants, to identify core protein modules associated with AD, race, sex, and age. Our analysis revealed ten co-expression modules linked to distinct biological pathways and cell types, many of which correlated with established AD biomarkers such as β-amyloid, tau, and phosphorylated tau. To further resolve disease heterogeneity, we applied a proteomic subtyping approach, identifying six distinct CSF subtypes spanning the clinical and pathological spectrum. These subtypes were validated

SUBMITTER: Bangs MC 

PROVIDER: S-EPMC11952530 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature