The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease.

ABSTRACT: Innate immunity is associated with Alzheimer's disease¹, but the influence of immune activation on the production of amyloid-β is unknown^2,3. Here we identify interferon-induced transmembrane protein 3 (IFITM3) as a γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-β. Inflammatory cytokines induce the expression of IFITM3 in neurons and astrocytes, which binds to γ-secretase and upregulates its activity, thereby increasing the production of amyloid-β. The expression of IFITM3 is increased with ageing and in mouse models that express familial Alzheimer's disease genes. Furthermore, knockout of IFITM3 reduces γ-secretase activity and the formation of amyloid plaques in a transgenic mouse model (5xFAD) of ea

SUBMITTER: Hur JY 

PROVIDER: S-EPMC7919141 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature