Microglia initially seed and later reshape amyloid plaques in Alzheimer’s disease

Abstract

AbstractWe demonstrate the dual role of microglia in Alzheimer’s disease (AD), initially harmful, by seeding amyloid plaques, and protective in later stages by compacting amyloid plaques. Early microglial depletion using pharmacological or genetic blockage of CSF1R reduces plaque load and associated neuritic dystrophy, while human microglia transplantation restores plaque formation, confirming their seeding role. TransplantedTREM2R47H/R47Hmicroglia exacerbate plaque pathology, highlighting microglia as key initiators of the amyloid pathology cascade.