When Aβ is injected into the rat CNS, microglia are observed to contain the injected peptide, demonstrating their ability to take up Aβ [126]. However, in-vitro evidence suggests that this phagocytic ability is inhibited during disease [127]. The ability of microglia to phagocytize Aβ may depend on their phenotype. For example, in-vitro treatment of microglia with the pro M1 activator lipopolysaccharide inhibited microglial phagocytosis of Aβ [127]. Other proinflammatory cytokines, such as IFNγ and TNFα not only inhibited uptake of Aβ, but also prevented internalized Aβ degradation [128,129]. This demonstrates that M1 microglia might be less able to properly take up and degrade Aβ. While M1 microglia appear to be impaired in their ability to remove Aβ, M2 microglia have been demonstrated to be efficient phagocytes. Treatment with the pro M2 activating cytokine IL-4 can effectively block lipopolysaccharide-induced inhibition of Aβ phagocytosis [127] and similar data have been obtained for IL-10 [129]. This effect also extends to degradation of the internalized Aβ. Treatment with IL-4 or macrophage colony-stimulating factor can lower the pH of the phagosome and lysosome and allow
