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

International Journal of Molecular Sciences
Pedram HonarpishehBhanu P Ganesh

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 IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral Aβ pathology. Lastly, we report Aβ deposition in the intestinal autopsy from AD patients with confirmed cerebral Aβ pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut ...Continue Reading

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Citations

Sep 29, 2020·The Journal of Physiology·Ilan Vonderwalde, Emma Finlayson-Trick
Feb 14, 2021·Biomolecules·Maria Jose Carranza-NavalAngel Del Marco
Mar 16, 2021·Frontiers in Immunology·Amanda L MillerÇagla Tükel
Jun 15, 2021·Frontiers in Aging Neuroscience·Shaochang WuZongxin Ling
Mar 17, 2021·Reviews in the Neurosciences·Kian Chung ChokSoi Moi Chye

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Methods Mentioned

BETA
transgenic
IECs
genotyping
Assay
PCR

Software Mentioned

UCLUST
MILLIPLEX ® Analyst
ATIMA ( Agile Toolkit for Incisive Microbial Analyses )
SPSS
Vision
Agilent quantitative
ChimeraSlayer
QIIME
Agilent Mass hunter
Quantitative Insights Into Microbial Ecology ( QIIME

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