Get started
Work

Transmission of Alzheimer’s disease-associated microbiota dysbiosis and its impact on cognitive function: evidence from mice and patients

Year: 2023
Type: article
Abstract: Spouses of Alzheimer’s disease (AD) patients are at higher risk of developing AD dementia, but the reasons and underlying mechanism are unknown. One potential factor is gut microbiota dysbiosis, which has been associated with AD. However, it remains unclear whether the gut microbiota dysbiosis can be transmitted to non-AD individuals and contribute to the development of AD pathogenesis and cognitive impairment. The present study found that co-housing wild-type mice with AD transgenic mice or giving them AD transgenic mice feces caused AD-associated gut microbiota dysbiosis, Tau phosphorylation, and cognitive impairment. Gavage with Lactobacillus and Bifidobacterium restored these changes. The oral and gut microbiota of AD patient partners resembled that of AD patients but differed from healthy controls, indicating the transmission of oral and gut microbiota and its impact on cognitive function. The underlying mechanism of these findings includes that the butyric acid-mediated acetylation of GSK3β at lysine 15 regulated its phosphorylation at serine 9, consequently impacting Tau phosphorylation. These results provide insight into a potential link between gut microbiota dysbiosis and AD and underscore the need for further research in this area.
DOI: 10.1038/s41380-023-02216-7
Authors: Yiying Zhang, Yuan Shen, Ning Liufu, Ling Liu, Wei Li, Zhongyong Shi, Hailin Zheng, Xinchun Mei, Chih-Yu Chen, Zengliang Jiang, Shabnamsadat Abtahi, Yuanlin Dong, Feng Liang, Yujiang Shi, Leo L. Cheng, Guang Yang, Jing X. Kang, Jeremy E. Wilkinson, Zhongcong Xie
Institutions: Harvard University, Massachusetts General Hospital, Tongji University, Shanghai Jiao Tong University, Shanghai Tenth People's Hospital, Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Westlake University, Shanghai Medical College of Fudan University, Fudan University, Zhongshan Hospital, Columbia University Irving Medical Center
Language: English
Open Access status: green
Funders: Foundation for the National Institutes of Health, Harvard University, Harvard T.H. Chan School of Public Health, Ludwig Institute for Cancer Research, University of Oxford, National Institutes of Health, National Institute on Aging
Awards: Microbiome Dysbiosis and Postoperative Delirium Pathogenesis, G3089139215, G33832021, Postoperative Delirium and Alzheimer's Disease Related Dementias, G6058849600, G6699223803, G7044538391, Pathogenesis of Postoperative Cognitive Dysfunction
OpenAlex ID: W4386028473
FWCI: 6.575
Cites: 100
Cited by: 83
Related to: 10