Excretion of Amyloid-β in the Gastrointestinal Tract and Regulation by the Gut Microbiota

Article type: Research Article

Authors: Wu, Shijing^{a; 1} | Hu, Li^{a; b; 1} | Lin, Jiajing^{c; 1} | Li, Kanglan^d | Ye, Shicai^e | Zhu, Shaoping^{f; *} | Liu, Zhou^{a; *}

Affiliations: [a] Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China | [b] Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, Guangdong, China | [c] Department of Psychiatry, Maoming People’s Hospital, MaoMing, Guangdong, China | [d] Department of Pharmacy, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, Guangdong, China | [e] Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China | [f] Institute of Laboratory Animal Center, Guangdong Medical University, Zhanjiang, Guangdong, China

Correspondence: [*] Correspondence to: Shaoping Zhu, Institute of Laboratory Animal Center, Guangdong Medical University, Zhanjiang, Guangdong 524001, China. E-mail: spzhu@gdmu.edu.cn. and Zhou Liu, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China. Tel.: +86 13543558835; E-mail: liuzhou@gdmu.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Amyloid-β (Aβ) is important in the etiology of Alzheimer’s disease (AD). Removal of Aβ from the brain is a major strategy for the prevention and treatment of AD. Objective:To clarify whether Aβ42 can be cleared by intestinal excretion and whether the gut microbiota (GM) can affect the excretory clearance of Aβ42 in the peripheral blood and intestines. Methods:Male 8-month-old C57BL6 mice were maintained on either normal chow or received broad-spectrum antibiotics in their drinking water for one week. Sterile saline, fluorescein isothiocyanate (FITC), or FITC-Aβ42 (fluorescein isothiocyanate-labeled amyloid-β42 peptides) was injected 1 h before sampling. Related changes of Aβ42 before and after injection were evaluated. Results:FITC-Aβ42 was injected into mice through the tail vein and could later be detected in feces. Furthermore, the fecal concentrations of FITC-Aβ42 were higher in mice that had been fed antibiotics to alter their GM than in normal mice. However, the FITC-Aβ42 concentrations in blood showed the opposite pattern. Conclusion: Aβ42 can be excreted into the intestinal lumen and is regulated by the GM.

Keywords: Alzheimer’s disease, amyloid-β , antibiotics, excretion of Aβ , gut microbiota

DOI: 10.3233/JAD-220705

Journal: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1153-1162, 2022