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Research Paper|Volume 12, Issue 11|pp 10912—10930

Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer’s disease patients, animal models and cell models

Zhimin Long1,2, Jingfei Chen1, Yueyang Zhao1, Wen Zhou3, Qiuhui Yao1, Yingxiong Wang4, Guiqiong He1,2
  • 1Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China
  • 2Department of Anatomy, Chongqing Medical University, Chongqing 400016, China
  • 3Department of Neurorehabilitation, The Affiliated Rehabilitation Hospital of Chongqing Medical University, Chongqing 400016, China
  • 4Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing 400016, China
Received: December 9, 2019Accepted: March 30, 2020Published: June 13, 2020
https://doi.org/10.18632/aging.103305

Copyright © 2020 Long et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Autophagy has been reported to play a dual "double-edged sword" role in the occurrence and development of Alzheimer’s disease (AD). To assess the relationship between AD and autophagy, the dynamic changes of autophagic flux in the brain of postmortem AD patients, animal models and cell models were studied. The results showed that autophagosomes (APs) accumulation and expression of lysosomal markers were decreased in the brains of AD patients. In the brain of APP/PS1 double transgenic mice, APs did not accumulate before the formation of SPs but accumulated along with the deposition of SPs, as well as the level of lysosomal markers cathepsin B and Lamp1 protein decreased significantly. In the brains of APP/PS1/LC3 triple - transgenic mice, the number of APs increased with age, but the number of ALs did not increase accordingly. The activation of autophagy is mainly due to the increase in Aβ rather than the overexpression of mutated APP gene. However, both the treatment with exogenous Aβ25-35 and the mutation of the endogenous APP gene blocked the fusion of APs with lysosomes and decreased lysosomal functioning in AD model cells, which may be the main mechanism of autophagy dysregulation in AD.