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

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.