| Project/Area Number |
24591246
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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 |
Neurology
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | amyloid / lipid rafts / synapse / tau / Alzheimer / ｆｙｎ / NMDA receptor / シナプス / Aβ / oligomer / fyn / prion / synaptosome / アルツハイマー病 / アミロイド / プリオン / レビー小体型認知症 / リピドラフト / 信号伝達 / オリゴマー / シヌクレイン / NMDA受容体 |
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| Outline of Final Research Achievements |
In lipid rafts from AD model mice, Tg2576 brains, Aß oligomers formed complex with cellular prion protein. Aß oligomers, fyn, NMDA receptor subunits, GSK3ß, and phosphorylated tau, all localized in lipid rafts. To analyze the relation between Aß dimers and tauopathy in lipid rafts, we established double APP-Tau Tg mice by mating Tg2576 and TgTauP301L. Phosphorylated tau and phosphorylation enzyme of tau, GSK3ß were increased clearly in lipid rafts from double Tg. Fyn and phosphorylated NMDA receptor subunit were also increased in lipid rafts from double Tg. Aß oligomers were suggested to induce phosphorylated tau and activate Fyn-NMDA pathway in lipid rafts.
In synaptosomes fraction, Aß oligomers and phosphorylated tau were detected. In synaptosomes from Tg2576 brains, phosphorylated tau was much increased compared to that from nontransgenic brains. Induction of phosphorylated tau may occur in synapse.
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