| Project/Area Number |
26893337
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Saito Satoshi 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (40732996)
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アルツハイマー型認知症 / Aβ / Tau / 脳アミロイド血管症 / クリアランス / アルツハイマー病 / タウ |
|---|
| Outline of Final Research Achievements |
β-amyloid (Aβ) is partially cleared through perivascular drainage pathway (PVD). The disturbance of PVD is a common finding in sporadic Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) patients. We hypothesized that tau is eliminated through PVD, and investigated the role of CAA in the tau metabolism.
We developed double transgenic mice by crossbreeding PS19 mice carrying the MAPT gene with P301S mutation with CAA model mice expressing the APP gene with Swedish-Dutch-Iowa mutations, in which Aβ clearance was severely impaired. Immunohistochemical staining showed that the amount of Aβ, total tau, 4 repeat tau, and hyperphosphorylated tau was significantly elevated in the double Tg mice compared with the other mouse groups.
Tau metabolism is closely associated with cerebrovascular integrity. Neurovascular approach is warranted for AD and CAA treatment.
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