Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-/- knock-out mice.
Direct immunization with amyloid beta protein (Abeta) and passive transfer of anti-Abeta antibodies reduce Abeta accumulation and attenuate cognitive deficits in transgenic models of Alzheimer's disease (AD). The reduction in Abeta deposition has been proposed to involve microglial phagocytosis of Abeta immune complexes via Fc receptors (FcRs). We have examined the efficacy of Abeta immunization in amyloid precursor protein (APP) transgenic mice crossed into FcR-gamma chain knock-out mice (FcRgamma-/-). As might be expected from previous studies on macrophages, phagocytosis of Abeta immune complexes via FcR was completely impaired in microglia cells isolated from FcRgamma-/- mice. Thus, we immunized APP Tg2576 transgenic mice that were crossed in the FcRgamma-/- background with Abeta1-42 and then analyzed the effect on Abeta accumulation. In APP Tg2576 transgenic mice crossed to FcRgamma-/-, Abeta1-42 immunization significantly attenuated Abeta deposition, as assessed by both biochemical and immunohistological methods. The reduction in Abeta accumulation was equivalent to the reduction in deposition seen in Abeta1-42 immunized, age-matched, FcR-sufficient Tg2576 mice. We conclude that after Abeta immunization, the effects of anti-Abeta antibodies on Abeta deposition in APP Tg2576 transgenic mice are not dependent on FcR-mediated phagocytic events.
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000682:Amyloid / Q000276:immunology* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000032:analysis; D000936:Antigen-Antibody Complex / Q000378:metabolism; D002478:Cells, Cultured; D003433:Crosses, Genetic; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D058225:Plaque, Amyloid / Q000473:pathology; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000906:Antibodies; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D010446:Peptide Fragments; D017452:Receptors, IgG; C075222:amyloid beta-protein (1-42)