Microglial Rack1 Deficiency Alleviates Alzheimer's Disease Pathology through Enhancing IGF1-Mediated Astrocytic Phagocytosis.

ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disorder. Microglia make significant contributions to neuroinflammation and the progression of AD. However, the regulatory role of microglial activation and the communication between microglia and astrocytes in AD are largely unknown. Here, it is found that Rack1 levels are elevated in microglia of patients with AD and AD model mice. The conditional knockout of Rack1 in microglia reduced Aβ aggregation, alleviated neuroinflammation, and rescued cognitive impairments in AD model mice. Mechanistically, the knockout of Rack1 in microglia decreased the number of microglia while increasing both the numbers and phagocytic activities of astrocytes by upregulating the levels of IGF1. The inhibition of IGF1R blocked microglial Rack1 defi

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12806348 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature