Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice.

ABSTRACT: Amyloid plaques in Alzheimer's disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (Aβ) pathogenesis; however, the mechanisms are still not well understood. We hypothesize that the gut bears the Aβ burden prior to brain, highlighting gut-brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular Aβ deposition in the IEB occur before cerebral Aβ aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including

SUBMITTER: Honarpisheh P 

PROVIDER: S-EPMC7084806 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature