Gastrointestinal Dysfunction and Low-Grade Inflammation Associate With Enteric Neuronal Amyloid-β in a Model for...

Area of Science:

• Neuroscience
• Gastroenterology
• Pathology

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder causing cognitive decline.
• Patients with AD often experience gastrointestinal (GI) problems.
• Gut alterations may influence AD pathology, necessitating research into brain-gut interactions.

Purpose of the Study:

• To investigate the link between Alzheimer's disease and gastrointestinal dysfunction.
• To characterize the pathological changes in the GI tract of 5xFAD mice, an AD model.

Main Methods:

• Detailed pathological analysis of the GI tract in 5xFAD mice.
• Histological analyses, gene expression studies, immunofluorescence labeling, and gut function assays were performed.

Main Results:

• Elevated intestinal amyloid precursor protein and amyloid-beta (Aβ) accumulation in enteric neurons were observed in 5xFAD mice.
• Mild intestinal inflammation, fibrosis, and increased proinflammatory cytokines were associated with Aβ accumulation.
• 5xFAD mice exhibited accelerated gastrointestinal transit.

Conclusions:

• Amyloid-beta accumulation in enteric neurons is linked to low-grade intestinal inflammation and altered gut motility.
• Peripheral pathology in Alzheimer's disease may contribute to gastrointestinal dysfunction in patients.