Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

作者：Jun Wang, Bin‐Lu Sun, Yang Xiang, Ding‐Yuan Tian, Chi Zhu, Weiwei Li, Yu-Hui Liu, Xian‐Le Bu, Lin‐Lin Shen, Wang‐Sheng Jin, Zhen Wang, Gui‐Hua Zeng, Wei Xu, Liyong Chen, Xiaowei Chen, Zhian Hu, Zhiming Zhu, Weihong Song, Huadong Zhou, Jin‐Tai Yu, Yan‐Jiang Wang · 发表于：Translational Psychiatry · 年份：2020 · DOI：10.1038/s41398-020-00918-y · 被引用次数：86 · 研究领域：Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms、Biochemical Analysis and Sensing Techniques

Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.