Multiple inflammatory pathways are involved in the development and progression of cognitive deficits in APPswe/PS1dE9 mice

Increased accumulation of amyloid-beta peptide (A beta) and neuroinflammation is known to exist within the Alzheimer's disease (AD) brain. However, it remains unclear which form of A beta pathologies triggers neuroinflammation and whether increased neuroinflammation contributes to cognitive deficits in AD. In the present study we found that increased inflammatory responses might occur early in preplaque APPswe/PS1dE9 mice, and were significantly enhanced in both early-and late-plaque APPswe/PS1dE9 mice. Correlational analysis revealed that multiple inflammatory indexes significantly correlated with soluble A beta level, rather than amyloid plaque burden or insoluble A beta level, in APPswe/PS1dE9 mice. Moreover, multiple inflammatory indexes highly correlated with the impaired spatial learning and memory in APPswe/PS1dE9 mice. Collectively, these results provide evidence that inflammatory responses might be likely triggered by soluble toxic A beta species. Importantly, we demonstrate for the first time that multiple inflammatory pathways might be involved in the development and progression of cognitive deficits in APPswe/PS1dE9 mice, suggesting that a pharmacological approach targeting multiple inflammatory pathways may be a novel promising strategy to prevent or delay AD. (C) 2012 Elsevier Inc. All rights reserved.