alternative activation, amyloid deposition, immunotherapy, microglia, neuroinflammation
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.
Digital Object Identifier (DOI)
Citation / Publisher Attribution
ASN Neuro, v. 3, issue 5, art. e00069
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http:// creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
Scholar Commons Citation
Wilcock, Donna M.; Zhao, Qun; Morgan, Dave; Gordon, Marcia N.; Everhart, Angela; Wilson, Joan G.; Lee, Jennifer E.; and Colton, Carol A., "Diverse Inflammatory Responses in Transgenic Mouse Models of Alzheimer's Disease and the Effect of Immunotherapy on These Responses" (2011). Molecular Pharmacology & Physiology Faculty Publications. 5.
Was this content written or created while at USF?