Proposed mechanisms of action of immunotherapy in amyloid reduction. Panel A describes the mechanism of microglial phagocytosis. Amyloid fibers opsonized by antibodies enter the brain from the bloodstream where microglial cells recognize the antibodies and phagocytose the amyloid via the Fcg receptor. Panel B represents the mechanism of catalytic disaggregation. Amyloid fibers are bound by antibodies that disrupt the tertiary structure of the amyloid deposit. This results in solubilization of the Ab and exit of the brain. Panel C shows the peripheral sink mechanism. In this case, monomeric soluble Ab circulating in the bloodstream is bound by the circulating antibodies. This sequestration of circulating Ab produces a shift in the concentration gradient of Ab between the brain and the blood causing an efflux of Ab out of the brain.