Quantitative Expression Analysis of APP Pathway and Tau Phosphorylation-Related Genes in the ICV STZ-Induced Non-Human Primate Model of Sporadic Alzheimer’s Disease

International Journal of Molecular Sciences

Sang-Je Park³  Young-Hyun Kim³  Gyu-Hwi Nam³  Se-Hee Choe³  Sang-Rae Lee³  Sun-Uk Kim³  Ji-Su Kim³  Bo-Woong Sim³  Bong-Seok Song³  Kang-Jin Jeong³  Youngjeon Lee³  Young Il Park¹  Kyoung-Min Lee²  Jae-Won Huh³  Kyu-Tae Chang³ 

[1] Graduate School Department of Digital Media, Ewha Womans University, Seoul 120-750, Korea; E-Mail:;Department of Neurology, Seoul National University Hospital, Seoul 110-744, Korea; E-Mail:;National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea; E-Mails:

关键词: Alzheimer’s disease;    streptosozocin;    cynomolgus monkey;    qPCR;    APP;    tau;   

DOI  :  10.3390/ijms16022386

来源: mdpi

【 摘 要 】

The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ) and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer’s disease (AD). Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD) research using intracerebroventricular administration of streptozotocin (icv STZ). To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP) pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1) and cyclin-dependent kinase 5 (CDK5), all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.