| 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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