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

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Title
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
Author(s)
Sang Je ParkYoung-Hyun Kim; Gyu-Hwi Nam; Se Hee Choe; Sang-Rae LeeSun-Uk KimJi-Su KimBo Woong SimBong Seok SongKang Jin JeongYoungjeon Lee; Y I Park; K M Lee; Jae Won Huh; Kyu Tae Chang
Bibliographic Citation
International Journal of Molecular Sciences, vol. 16, no. 2, pp. 2386-2402
Publication Year
2015
Abstract
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.
Keyword
Alzheimer’s diseaseAPPCynomolgus monkeyqPCRStreptosozocinTau
ISSN
1422-0067
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms16022386
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
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