在 EFAD-Tg 小鼠中，APOE4通过钙蛋白酶CDK5通路诱导位点专一tau蛋白磷酸化

Title:APOE4 Induces Site-Specific Tau Phosphorylation Through Calpain-CDK5 Signaling Pathway in EFAD-Tg Mice

Volume: 13 Issue: 9

Author(s): Meng Zhou, Tianwen Huang, Nicole Collins, Jing Zhang, Hui Shen, Xiaoman Dai, Naian Xiao, Xilin Wu, Zhen Wei, Jason York and Lanyan Lin, Yuangui Zhu, Mary Jo LaDu, Xiaochun Chen

Affiliation:

关键词: 载脂蛋白E，β淀粉样蛋白，阿尔茨海默病，钙蛋白酶CDK5，EFAD小鼠，磷酸化

摘要: APOE4 is the greatest genetic risk factor for Alzheimer’s disease (AD), particularly associated with increased levels of amyloid-β (Aβ) and amyloid deposition. However, it remains unclear whether APOE4 is associated with greater tau phosphorylation and neurofibrillary tangle formation, a hallmark of AD leading to structural disruption of the neuronal cytoskeleton. The current study used 3 and 7 month old EFAD mice, which express human APOE and over-express specifically human Aβ42 via 5 familial-AD (FAD) mutations, to investigate APOE genotype-specific effects on site-specific tau phosphorylation. The results reveal that AD-like site-specific tau phosphorylation was increased in E4FAD mice, accompanied by disrupted cortical neuronal morphology, compared to E3FAD mice. Further analysis demonstrated that the levels of CDK5, its regulatory subunits (p35 and p25) and calpain (including calpain1 and calpain2), but not GSK3β, were significantly increased in E4FAD mice compared to E3FAD mice. These results suggest that the APOE4 genotype contributes to increased site-specific tau phosphorylation via activation of the calpain-CDK5 signaling pathway.

Cite this article as:

Meng Zhou, Tianwen Huang, Nicole Collins, Jing Zhang, Hui Shen, Xiaoman Dai, Naian Xiao, Xilin Wu, Zhen Wei, Jason York and Lanyan Lin, Yuangui Zhu, Mary Jo LaDu, Xiaochun Chen , APOE4 Induces Site-Specific Tau Phosphorylation Through Calpain-CDK5 Signaling Pathway in EFAD-Tg Mice, Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205013666160415154550