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Research Paper|Volume 11, Issue 22|pp 10242—10251

Studies on APP metabolism related to age-associated mitochondrial dysfunction in APP/PS1 transgenic mice

Lizhi Chen1, Shicheng Xu2, Tong Wu3, Yijia Shao3, Li Luo4, Lingqi Zhou3, Shanshan Ou3, Hai Tang5, Wenhua Huang1, Kaihua Guo3, Jie Xu3
  • 1Department of Clinical Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
  • 2Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
  • 3Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
  • 4Department of Anatomy, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, China
  • 5Department of Anatomy, Guangdong Jiangmen Chinese Traditional Medicine College, Jiangmen, China
* Equal contribution
Received: March 25, 2019Accepted: November 7, 2019Published: November 19, 2019
https://doi.org/10.18632/aging.102451

Copyright © 2019 Chen 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

The aging brain with mitochondrial dysfunction and a reduced adenosine 5’-triphosphate (ATP) has been implicated in the onset and progression of β-Amyloid (Aβ)-induced neuronal toxicity in AD. To unravel the function of ATP and the underlying mechanisms on AD development, APP/PS1 double transgenic mice and wild-type (WT) C57 mice at 6 and 10 months of age were studied. We demonstrated a decreased ATP release in the hippocampus and platelet of APP/PS1 mice, comparing to C57 mice at a relatively early age. Levels of Aβ were raised in both hippocampus and platelet of APP/PS1 mice, accompanied by a decrease of α-secretase activity and an increase of β-secretase activity. Moreover, our results presented an age-dependent rise in mitochondrial vulnerability to oxidation in APP/PS1 mice. In addition, we found decreased pSer473-Akt levels, increased GSK3β activity by inhibiting phosphorylation at Ser9 in aged APP/PS1 mice and these dysfunctions probably due to down-regulation of Bcl-2 and up-regulation of cleaved caspase-3. Therefore, we demonstrate that PI3K/Akt/GSK3β signaling pathway could be involved in Aβ-associated mitochondrial dysfunction of APP/PS1 mice and APP abnormal metabolism in platelet might provide potential biomarkers for early diagnosis of AD.