Gut Inflammation Regulates A? and Tau Fibril Propagation to brain via a C/EBP?/?-secretase Pathway

ABSTRACT: Inflammation plays an important role in Alzheimer's disease (AD). We applied chronic administration of 1% DSS or colonic injection of A? or Tau fibrils or AD patient brain lysates in 3xTg mice and combined it with a vagotomy procedure aiming at exploring the role of gut-brain axis in the development of AD-like pathologies. C/EBP?/?-secretase signaling is temporally activated in the gut of AD patients and 3xTg mice, initiating A? and Tau fibril formation spreading to the brain. DSS treatment promotes gut leakage and facilitates AD-like pathologies in both the gut and the brain of 3xTg mice in a C/EBP?/?-secretase-dependent manner. Vagotomy selectively blunts this signaling, attenuates A? and tau pathologies and restores learning and memory. Colonic injected A? or Tau fibrils or AD patient

SUBMITTER: Chun Chen 

PROVIDER: S-SCDT-EMBOJ-2020-106320 | biostudies-other |

REPOSITORIES: biostudies-other