IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid β precursor protein transgenic mice

Paramita Chakrabarty, Carolina Ceballos-Diaz, Amanda Beccard, Christopher Janus, Dennis W Dickson, Todd E. Golde, Pritam Das

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Reactive gliosis surrounding amyloid β (Aβ) plaques is an early feature of Alzheimer's disease pathogenesis and has been postulated to represent activation of the innate immune system in an apparently ineffective attempt to clear or neutralize Aβ aggregates. To evaluate the role of IFN-γ-mediated neuroinflammation on the evolution of Aβ pathology in transgenic (Tg) mice, we have expressed murine IFN-γ (mIFN-γ) in the brains of Aβ precursor protein (APP) Tg mice using recombinant adeno-associated virus serotype 1. Expression of mIFN-γ in brains of APP TgCRND8 mice results in robust noncell autonomous activation of microglia and astrocytes, and a concomitant significant suppression of Aβ deposition. In these mice, mIFN-γ expression upregulated multiple glial activation markers, early components of the complement cascade as well as led to infiltration of Ly-6c positive peripheral monocytes but no significant effects on APP levels, APP processing or steady-state Aβ levels were noticed in vivo. Taken together, these results suggest that mIFN-γ expression in the brain suppresses Aβ accumulation through synergistic effects of activated glia and components of the innate immune system that enhance Aβ aggregate phagocytosis.

Original languageEnglish (US)
Pages (from-to)5333-5343
Number of pages11
JournalJournal of Immunology
Volume184
Issue number9
DOIs
StatePublished - May 1 2010

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Protein Precursors
Amyloid beta-Protein Precursor
Amyloid Plaques
Transgenic Mice
Neuroglia
Immune System
Brain
Dependovirus
Gliosis
Microglia
Phagocytosis
Astrocytes
Monocytes
Alzheimer Disease
Pathology

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid β precursor protein transgenic mice. / Chakrabarty, Paramita; Ceballos-Diaz, Carolina; Beccard, Amanda; Janus, Christopher; Dickson, Dennis W; Golde, Todd E.; Das, Pritam.

In: Journal of Immunology, Vol. 184, No. 9, 01.05.2010, p. 5333-5343.

Research output: Contribution to journalArticle

Chakrabarty, Paramita ; Ceballos-Diaz, Carolina ; Beccard, Amanda ; Janus, Christopher ; Dickson, Dennis W ; Golde, Todd E. ; Das, Pritam. / IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid β precursor protein transgenic mice. In: Journal of Immunology. 2010 ; Vol. 184, No. 9. pp. 5333-5343.
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