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.
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.
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. parksj@kribb.re.kr.
authors.forename: Sang-Je
authors.initials: SJ
authors.lastname: Park
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. kyh@kribb.re.kr.
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. nkh14@kribb.re.kr.
authors.forename: Gyu-Hwi
authors.initials: GH
authors.lastname: Nam
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. csh91@kribb.re.kr.
authors.forename: Se-Hee
authors.initials: SH
authors.lastname: Choe
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. srlee@kribb.re.kr.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. sunuk@kribb.re.kr.
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. kimjs@kribb.re.kr.
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. embryont@kribb.re.kr.
authors.forename: Bo-Woong
authors.initials: BW
authors.lastname: Sim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. sbs6401@kribb.re.kr.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Song
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. nemo9426@kribb.re.kr.
authors.forename: Kang-Jin
authors.initials: KJ
authors.lastname: Jeong
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. neurosci@kribb.re.kr.
authors.forename: Youngjeon
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Graduate School Department of Digital Media, Ewha Womans University, Seoul 120-750, Korea. yipark@ewha.ac.kr.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Park
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 110-744, Korea. kminlee@snu.ac.kr.
authors.forename: Kyoung-Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. huhjw@kribb.re.kr.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Huh
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea. changkt@kribb.re.kr.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008252:Macaca fascicularis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D016875:tau Proteins; D013311:Streptozocin; D051360:Cyclin-Dependent Kinase 5; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053829:Amyloid Precursor Protein Secretases; D002154:Calpain