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

Background: Amyloid-beta (A beta) is important in the etiology of Alzheimer's disease (AD). Removal of A beta from the brain is a major strategy for the prevention and treatment of AD. Objective: To clarify whether A beta(42) can be cleared by intestinal excretion and whether the gut microbiota (GM) can affect the excretory clearance of A beta(42) 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 drinkingwater for one week. Sterile saline, fluorescein isothiocyanate (FITC), or FITC-A beta(42) (fluorescein isothiocyanatelabeled amyloid-beta(42) peptides) was injected 1 h before sampling. Related changes of A beta(42) before and after injection were evaluated. Results: FITC-A beta(42) was injected into mice through the tail vein and could later be detected in feces. Furthermore, the fecal concentrations of FITC-A beta(42) were higher in mice that had been fed antibiotics to alter their GM than in normal mice. However, the FITC-A beta(42) concentrations in blood showed the opposite pattern. Conclusion: A beta(42) can be excreted into the intestinal lumen and is regulated by the GM.