Microglia Mediate the Clearance of Soluble Aβ through Fluid Phase Macropinocytosis

摘要: Alzheimer's disease is characterized by the progressive deposition of beta-amyloid (Abeta) within brain parenchyma and its subsequent accumulation into senile plaques. Pathogenesis associated with perturbations in Abeta homeostasis inefficient clearance these soluble insoluble peptides from brain. Microglia have been reported to mediate fibrillar (fAbeta) through receptor-mediated phagocytosis; however, their participation (sAbeta) largely unknown. We report that microglia internalize sAbeta extracellular milieu a nonsaturable, fluid phase macropinocytic mechanism distinct phagocytosis endocytosis both vitro vivo. The uptake dependent on actin tubulin dynamics does not involve clathrin assembly, coated vesicles or membrane cholesterol. Upon internalization, fluorescently labeled colocalizes pinocytic vesicles. rapidly traffic late endolysosomal compartments where they are subject degradation. Additionally, we demonstrate fAbeta occurs mechanisms upon internalization segregated separate subcellular vesicular compartments. Significantly, found proteolytic degradation sAbeta, fluorescent chromophore retained microglial cell. These studies identify an important which cells participate maintenance homeostasis, capacity constitutively clear