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

Sang Je Park, Young Hyun Kim, Gyu Hwi Nam, Se Hee Choe, Sang Rae Lee, Sun Uk Kim, Ji Su Kim, Bo Woong Sim, Bong Seok Song, Kang Jin Jeong, Youngjeon Lee, Young Il Park, Kyoung Min Lee, Jae Won Huh, Kyu Tae Chang

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22 Scopus citations

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.

Original languageEnglish
Pages (from-to)2386-2402
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume16
Issue number2
DOIs
StatePublished - 22 Jan 2015

Bibliographical note

Publisher Copyright:
© 2015 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

  • APP
  • Alzheimer’s disease
  • Cynomolgus monkey
  • Streptosozocin
  • Tau
  • qPCR

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