Primary cilia-mediated regulation of microglial secretion in Alzheimer’s disease

Abstract

Graphical AbstractMicroglial phagocytosis and exocytosis of Aβ are mediated by primary cilia, which influence extracellular proteostasis, Aβ plaque formation, and neurite dystrophy. When microglia in wild-type mice develop into the disease-associated state, they require genes involved in primary ciliogenesis and extracellular vesicle secretion. Inhibition of Ift88, a key cilia gene, in microglia stimulates phagocytosis and the secretion of extracellular vesicles with an altered proteomic composition, leading to the failure of extracellular proteostasis and neurite degeneration.