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Macrophage colony stimulating factor (M-CSF) and its receptor are upregulated in the brain in Alzheimer's disease. M-CSF induces activation and proliferation of microglial cells and expression of proinflammatory cytokines. Amyloid beta (Aβ) immunization experiments suggest that microglia have the capacity to aggressively clear Aβ from the brain under certain circumstances. We examined the role of M-CSF in phagocytosis of fluorescent microspheres and Aβ by cultured microglia. M-CSF treatment increased microglial cell phagocytosis of both microspheres and of Aβ. Antibody neutralization of M-CSF inhibited Aβ uptake induced by overexpression of the M-CSF receptor on microglia. These results suggest that M-CSF could be important in promoting microglial clearance of abnormal protein aggregates such as Aβ.