Identification of modifier genes of Alzheimer's disease amyloid pathology using a mouse-to-human translational approach
| Project/Area Number |
23591706
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
MORIHARA Takashi 大阪大学, 医学(系)研究科(研究院), 助教 (90403196)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Masatoshi 大阪大学, 医学部精神医学教室, 教授 (00179649)
TANAKA Toshihisa 大阪大学, 医学部精神医学教室, 准教授 (10294068)
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| Co-Investigator(Renkei-kenkyūsha) |
AKATHU Hiroyasu 福祉村病院, 長寿医学研究所, 副所長
SUZUKI Toshiharu 北海道大学, 大学院薬学研究科, 教授
COLE Greg UCLA, Dept Neurology, Professor
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アルツハイマー病 / 疾患関連遺伝子 / 多因子疾患 / 遺伝子 / ゲノム / 細胞内輸送 / Aβ / カナダ / 米国 / リスク遺伝子 / アミロイドベータ / モデル動物 / トランスクリプトミクス / マイクロアレイ |
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| Research Abstract |
Alzheimer's disease (AD) is a common, complex neurological disease caused by numerous genetic and environmental factors making the identification of sporadic AD related genes difficult. To overcome these difficulties, we combined a mouse model of Abeta accumulation and transcriptomics, which simplifies the complexity, yet increases the statistical power for such a genetic screen, and identified Klc1 variant E as an Abeta accumulation modifier in vivo. Notably, these results translated to humans where the expression levels of KLC1 variant E in brain were significantly higher in AD than control subjects. To our knowledge, this is the first report linking splicing of Klc1 to disease, and strongly implicates transport defects as a major contributor to Abeta accumulation and AD pathology.
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Functional genetic variation at the NRGN gene and schizophrenia : evidence from a gene-based case-control study and gene expression analysis2012
Author(s)
Ohi K, Hashimoto R, Yasuda Y, Fukumoto M, Yamamori H, Umeda-Yano S, Okada T, Kamino K, Morihara T, Iwase M, Kazui H, Numata S, Ikeda M, Ohnuma T, Iwata N, Ueno S, Ozaki N, Ohmori T, Arai H, Takeda M
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Journal Title
Am J Med Genet B Neuropsychiatr Genet
Volume: 159B(4)
Pages: 405-13
Related Report
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[Journal Article] Functional genetic variation at the NRGN gene and schizophrenia: Evidence from a gene-based case-control study and gene expression analysis.2012
Author(s)
Ohi K, Hashimoto R, Yasuda Y, Fukumoto M, Yamamori H, Umeda-Yano S, Okada T, Kamino K, Morihara T, Iwase M, Kazui H, Numata S, Ikeda M, Ohnuma T, Iwata N, Ueno S, Ozaki N, Ohmori T, Arai H, Takeda M
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Journal Title
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume: 159B(4)
Pages: 405-13
DOI
Related Report
Peer Reviewed
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[Journal Article] Protein kinase C stabilizes X-linked inhibitor of apoptosis protein (XIAP) through phosphorylation at Ser(87) to suppress apoptotic cell death.2011
Author(s)
Kato K, Tanaka T, Sadik G, Baba M, Maruyama D, Yanagida K, Kodama T, Morihara T, Tagami S, Okochi M, Kudo T, Takeda M.
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Journal Title
Psychogeriatrics
Volume: 11
Pages: 90-97
DOI
Related Report
Peer Reviewed
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[Presentation] An approach to complex disease modifier genes and mouse-to-human translation: transcriptome analysis of mouse strains reveals Alzheimer disease modifier gene2013
Author(s)
T. Morihara, N. Hayashi, H. Akatsu, M. Silverman, M. Yokokoji, N. Kimura, M. Sato, K. Kamino, Y. Yamagichi, T. Tsunoda, T. Tanaka, M. Takeda
Organizer
American Society of Human Genetics (ASHG) 2013
Place of Presentation
Boston(USA)
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