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 pro-inflammatory 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.