Amyloid-β immunization effectively reduces amyloid deposition in FcRγ-/- knock-out mice

Pritam Das, Victor Howard, Nicole Loosbrock, Dennis Dickson, M. Paul Murphy, Todd E. Golde

Research output: Contribution to journalArticle

195 Scopus citations

Abstract

Direct immunization with amyloid β protein (Aβ) and passive transfer of anti-Aβ antibodies reduce Aβ accumulation and attenuate cognitive deficits in transgenic models of Alzheimer's disease (AD). The reduction in Aβ deposition has been proposed to involve microglial phagocytosis of Aβ immune complexes via Fc receptors (FcRs). We have examined the efficacy of Aβ immunization in amyloid precursor protein (APP) transgenic mice crossed into FcR-γ chain knock-out mice (FcRγ -/-). As might be expected from previous studies on macrophages, phagocytosis of Aβ immune complexes via FcR was completely impaired in microglia cells isolated from FcRγ-/- mice. Thus, we immunized APP Tg2576 transgenic mice that were crossed in the FcRγ-/- background with Aβ1-42 and then analyzed the effect on Aβ accumulation. In APP Tg2576 transgenic mice crossed to FcRγ -/-, Aβ1-42 immunization significantly attenuated Aβ deposition, as assessed by both biochemical and immunohistological methods. The reduction in Aβ accumulation was equivalent to the reduction in deposition seen in Aβ1-42 immunized, age-matched, FcR-sufficient Tg2576 mice. We conclude that after Aβ immunization, the effects of anti-Aβ antibodies on Aβ deposition in APP Tg2576 transgenic mice are not dependent on FcR-mediated phagocytic events.

Original languageEnglish (US)
Pages (from-to)8532-8538
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number24
StatePublished - Sep 17 2003

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Keywords

  • Alzheimer's disease
  • Fc receptor
  • Microglia
  • Scavenger receptor
  • Vaccination
  • β-amyloid protein

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Das, P., Howard, V., Loosbrock, N., Dickson, D., Murphy, M. P., & Golde, T. E. (2003). Amyloid-β immunization effectively reduces amyloid deposition in FcRγ-/- knock-out mice. Journal of Neuroscience, 23(24), 8532-8538.