Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid-β-Induced Pathogenesis of Alzheimer's Disease.

ABSTRACT: Innate immune activation plays a crucial role in the pathogenesis of Alzheimer's disease (AD) and related dementias (ADRD). The cytosolic DNA sensing pathway, involving cGAMP synthase (cGAS) and Stimulator of Interferon Genes (STING), has emerged as a key mediator of neurodegenerative diseases. However, the precise mechanisms through which cGAS activation influences AD progression remain poorly understood. In this study, we observed significant up-regulation of cGAS-STING signaling pathway in AD. Notably, this increase is primarily attributed to microglia, rather than non-microglial cell types. Using an inducible, microglia-specific cGAS knockout mouse model in the 5xFAD background, we demonstrated that deleting microglial cGAS at the onset of amyloid-β (Aβ) pathology profoundly restricts

SUBMITTER: He S 

PROVIDER: S-EPMC11948024 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature