Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses

Donna M. Wilcock, Qun Zhao, Dave Morgan, Marcia N. Gordon, Angela Everhart, Joan G. Wilson, Jennifer E. Lee, Carol A. Colton

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT-PCR (reverse transcription-PCR) and protein analysis to measure inflammatory responses ranging from proinflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only (APPSw) and amyloid deposits with progression to tau pathology and neuron loss [APPSw/NOS2 -/- (nitric oxide synthase 2 -/-)]. We also examined tissues from previously published immunotherapy studies. These studies were a passive immunization study in APPSw mice and an active vaccination study in APPSw/NOS2 -/- mice. Both studies have already been shown to lower amyloid load and improve cognition. We have found that amyloid deposition is associated with high expression of alternative activation and acquired deactivation genes and low expression of pro-inflammatory genes, whereas disease progression is associated with a mixed phenotype including increased levels of some classical activation factors. Immunotherapy targeting amyloid deposition in both mouse models resulted in decreased alternative inflammatory markers and, in the case of passive immunization, a transient increase in pro-inflammatory markers. Our results suggest that an alternative immune response favours retention of amyloid deposits in the brain, and switching away from this state by immunotherapy permits removal of amyloid.

Original languageEnglish
Pages (from-to)249-258
Number of pages10
JournalASN Neuro
Issue number5
StatePublished - 2011


  • Alternative activation
  • Amyloid deposition
  • Immunotherapy
  • Microglia
  • Neuroinflammation

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Neurology


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