Amyloid- Immunization Effectively Reduces Amyloid Deposition in FcR / Knock-Out Mice

Direct immunization with amyloid protein (A ) and passive transfer of anti-A antibodies reduce A accumulation and attenuate cognitive deficits in transgenic models of Alzheimer’s disease (AD). The reduction in A deposition has been proposed to involve microglial phagocytosis of A immune complexes via Fc receptors (FcRs). We have examined the efficacy of A immunization in amyloid precursor protein (APP) transgenic mice crossed into FcRchain knock-out mice (FcR / ). As might be expected from previous studies on macrophages, phagocytosis of A immune complexes via FcR was completely impaired in microglia cells isolated from FcR / mice. Thus, we immunized APP Tg2576 transgenic mice that were crossed in the FcR / background with A 1– 42 and then analyzed the effect on A accumulation. In APP Tg2576 transgenic mice crossed to FcR / , A 1– 42 immunization significantly attenuated A deposition, as assessed by both biochemical and immunohistological methods. The reduction in A accumulation was equivalent to the reduction in deposition seen in A 1– 42 immunized, age-matched, FcR-sufficient Tg2576 mice. We conclude that after A immunization, the effects of anti-A antibodies on A deposition in APP Tg2576 transgenic mice are not dependent on FcR-mediated phagocytic events.