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The Journal of Neuroscience, September 17, 2003, 23(24):8532-8538
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Amyloid- Immunization Effectively Reduces Amyloid Deposition in FcR -/- Knock-Out Mice
Pritam Das,
Victor Howard,
Nicole Loosbrock,
Dennis Dickson,
M. Paul Murphy, and
Todd E. Golde
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224
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 FcR- chain 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 A1–42 and then analyzed the effect on A accumulation. In APP Tg2576 transgenic mice crossed to FcR-/-, A1–42 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 A1–42 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.
Key words: Alzheimer's disease; -amyloid protein; Fc receptor; scavenger receptor; microglia; vaccination
Received June 4, 2003;
revised July 23, 2003;
accepted July 29, 2003.
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