Alzheimer's disease in the gut-Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player

Abstract

Alzheimer's disease (AD) affects around 33 million people worldwide, which makes it the most prominent form of dementia. The main focus of AD research has been on the central nervous system (CNS) for long, but in recent years, the gut gained more attention. The intestinal tract is innervated by the enteric nervous system (ENS), built of numerous different types of neurons showing great similarity to neurons of the CNS. It already has been demonstrated that the amyloid precursor protein, which plays a major role in AD pathology, is also expressed in these cells. We analyzed gut tissue of AD model mice (5xFAD) and the respective wild-type littermates at different pathological stages: pre-pathological, early pathological and late pathological. Our results show significant difference in function of the intestine of 5xFAD mice as compared to wild-type mice. Using a pathway array detecting 84 AD-related gene products, we found ApoA1 expression significantly altered in colon tissue of 5xFAD mice. Furthermore, we unveil ApoA1's beneficial impact on cell viability and calcium homeostasis of cultured enteric neurons of 5xFAD animals. With this study, we demonstrate that the intestine is altered in AD-like pathology and that ApoA1 might be one key player within the gut.

Keywords: A-beta; FoxA2; enteric nervous system; lipids.