Proteomic signatures of the <i>APOE</i> ε<i>4</i> and <i>APOE</i> ε<i>2</i> genetic variants and Alzheimer's disease.

ABSTRACT: The ε4 and ε2 alleles of the Apolipoprotein E (APOE) gene confer opposite genetic risks for Alzheimer's disease (AD), but their underlying molecular mechanisms remain poorly characterized in humans. To resolve this, we systematically profiled APOE-associated proteomic alterations across five cohorts-including the Global Neurodegeneration Proteomics Consortium (GNPC), BioFINDER-2, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Parkinson's Progression Markers Initiative (PPMI), and UK Biobank (UKB)-using SomaLogic and OLINK platforms in plasma and cerebrospinal fluid (CSF) from over 10,000 individuals. Using GNPC (plasma SomaLogic, N=4,045), we mapped a comprehensive APOE-protein network and applied mediation modeling to classify genotype-related signals as

SUBMITTER: Lu L 

PROVIDER: S-EPMC12340876 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature