Distinct glial functions are associated with Alzheimer's disease based on cell-type- and pathway-specific polygenic risk score analysis.

ABSTRACT: BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, amyloid plaques, neurofibrillary tangles, and neuroinflammation. Glial cells-astrocytes, microglia, and oligodendrocytes-play essential roles in AD progression, but their pathway-specific genetic contributions remain unclear.ObjectiveTo identify glial cell type-specific biological pathways associated with AD using pathway-based polygenic risk score (PRS) analysis.MethodsWe applied PRSet to evaluate associations between glial-specific pathways and AD in a discovery dataset (ADc1234ADA), adjusting for the top two principal components (Model 1), and additionally for sex, age, and APOE ε4 status (Model 2). Pathways with nominal significance (p < 0.05) were further tested in an i

SUBMITTER: Pratt T 

PROVIDER: S-EPMC12417609 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature