A combination of indomethacin and atorvastatin ameliorates cognitive and pathological deterioration in PrP-hAβPPswe/PS1 ΔE9 transgenic mice.

Mounting evidence has shown that inflammation might drive Alzheimer's disease (AD) pathology and contribute to its exacerbation. Previous studies have indicated that indomethacin or atorvastatin are beneficial in treating AD; however, no significant clinical effects have been shown. Furthermore, no study has investigated the efficacy of combining these agents for treating AD. This study sought to determine the effect of a combination of indomethacin and atorvastatin in the PrP-hAβPPswe/PS1 ^ΔE9 (APP/PS1) transgenic AD mouse model. Treatment with indomethacin and atorvastatin ameliorated impairments in spatial learning and memory, and the active avoidance response in APP/PS1 mice. Moreover, we found a suppression of Aβ plaques and decreased concentration of Aβ _1-42 in the hippocampus of APP/PS1 mice following treatment. In addition, indomethacin and atorvastatin ameliorated abnormal cytokine secretion, lymphocyte subset disorder, and hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis imbalances in APP/PS1 mice. The combination of indomethacin and atorvastatin restored immune and neuroendocrine processes, attenuated pathologic changes and cognitive impairments in APP/PS1 transgenic mice, and could thus be a potential therapeutic agent for AD.
(Copyright © 2019. Published by Elsevier B.V.)