Research Paper Volume 11, Issue 19 pp 8642—8663
Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: a potential therapeutic approach for Alzheimer’s disease
- 1 Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
- 2 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
- 3 Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
Received: July 5, 2019 Accepted: September 27, 2019 Published: October 14, 2019https://doi.org/10.18632/aging.102352
How to Cite
Copyright © 2019 Gao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota, has been implicated in the pathogenesis of Alzheimer’s disease (AD). However, the mechanisms by which TMAO influence cognitive and pathological processes in the AD have not been investigated. In this study, we found that the circulating TMAO levels displayed an age-related increase in both WT and APP/PS1 mice and association with AD-like behavioral and pathological profile. Reduced TMAO by 3,3-Dimethyl-1-butanol (DMB) treatment ameliorated the cognitive deterioration and long-term potentiation (LTP) in APP/PS1 mice. Moreover, DMB treatment also induced a decrease in the Amyloid-β (Aβ)1-42, β-secretase, and β-secretase-cleaved C-terminal fragment (βCTF) levels in the hippocampus. Finally, the effects obtained after treatment with DMB were accompanied by a reduction in circulating clusterin levels and hippocampal neuroinflammatory status in APP/PS1 mice. These findings demonstrate that elevated circulating TMAO during the aging process might deteriorate cognitive function and pathology in APP/PS1 mice.