An experimental study to explore the pathogenetic mechanism of senile plaque formation and neurofibrillar degeneration in Alzheimer's disease
| Project/Area Number |
07670740
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
NONAKA Ikuya National Center of Neurology and Psychiatry, Ultrastructural Research, Director, 神経研究所・微細構造研究部, 部長 (80040210)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Osamu National Center of Neurology and Psychiatry, Ultrastructural Research, researche, 神経センター神経研究所・微細構造研究部, 研究員
GOTO Yu-ichi National Center of Neurology and Psychiatry, Ultrastructural Research, Head, 神経センター神経研究所・微細構造研究部, 室長 (20225668)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | rimmed vacuoles / tau / Alzheimmer's disease / beta-APP / myopathies / chloroquine / rimmed vacuole / β-アミロイド / チューブリン / 熱ショック蛋白70 / アポリポ蛋白E |
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| Research Abstract |
"Rimeed vacuole" characterized by intracytoplasmic small vacuoles rimmed by granular materials is seen in various disorders, especially distal myopathies and inclusion body myositis. In fibers with the rimmed vacuoles, Congo-red positive materaial which are positive to anti-beta APP,anti-tau and anti-prion protein antibodies is accumulated as seen in the brain with Alzheimer's disease. Tp study how beta APP and tau proteins are accumulated in the rimmed vacuoles, we have done the present study.
In skeletal muscle of the rat treated with choroquine, a well-known anti-malaria drug, rimmed vacuoles began to appear 6 weeks after the initiation of this treatment. After 12 week-treatment, almost all fibers had the vacuoles predominantly in the soleus muscle. In these fibers, accumulation of beta AP,beta APP,tau, tubulin and HSP70 proteins was immunohistochamically defected and increased in amount with time. Most of tau protein was phosphorylated. However, amyoloid fibrils were not defected on an electron microscopy.
The overall experimental results were quite similar to protein accumulation in the plaques of Alzheimer's brain. Therefore, choloroquine treated rat may provide a good experimental animal model to know how the protein is degrated in Alzheimer's disease.
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Report
(3 results)
Research Products
(11 results)
