Process and mechanism of microglial phagocytosis of amyloid-β peptide

One of the hallmarks of Alzheimer's disease is the accumulation of amyloid-(3 (A(3) fibrils associated with microglia. Recently, it has been suggested that microglial phagocytosis of Ap is one of the Ap clearance pathways in the brain. However, the mechanism of microglial phagocytosis of Ap remains obscure. In this study, we investigated this mechanism using cultured rat microglia. After exposure to Ap, Ap was detected at the cell surface of microglia, and then marked immunoreactivity was observed in the cytosolic vesicles. The microglial cell shape rapidly changed to an ameboid form during the process of phagocytosis. Although neither N-WASP nor WISH immunoreactivity was co-localized with F-actin, both WAVE and Racl immunoreactivity was cc-localized with F-actin in the lamellipodia of phogocytic microglia. In addition, treatment of cytochalasin D, an inhibitor of actin assembly, inhibited microglial phagocytosis of Ap. These results suggest that formation of F-actin is essential for microglial phagocytic function, and that WAVE and Racl may participate in the microglial phagocytosis of