Research Paper Volume 11, Issue 22 pp 10242—10251
Studies on APP metabolism related to age-associated mitochondrial dysfunction in APP/PS1 transgenic mice
- 1 Department of Clinical Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- 2 Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- 3 Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
- 4 Department of Anatomy, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- 5 Department of Anatomy, Guangdong Jiangmen Chinese Traditional Medicine College, Jiangmen, China
Received: March 25, 2019 Accepted: November 7, 2019 Published: November 19, 2019https://doi.org/10.18632/aging.102451
How to Cite
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.
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.