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An experimental study to explore the pathogenetic mechanism of senile plaque formation and neurofibrillar degeneration in Alzheimer's disease

Research Project

Project/Area Number 07670740
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry

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)

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)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
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)
Keywordsrimmed 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
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.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Murakami N,Ihara Y,Nonaka I: "Chloroquine treated rat : a possible model for Alzheimer's disease" Muscle Nerve. 18. 123-125 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami Goto Y,Itoh M,Katsumi Y,Wada Y,Ozawa E,Nonaka I: "Sarcolemmal indentation in cardiomyopathy with mental retardation and vacuolar myopathy" Neuromusc Disord. 5. 149-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kiyomoto BH,Murakami N,Kishibayashi J,Sunohara N,Nonaka I: "Readucing bodies in distal myopathy with rimmed vacuole formation" Acta Neuropathol. 89. 109-111 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami N,Ihara Y,Nonaka I: "Muscle fiber degeneration in distal myopathy with rimmed vacuole formation" Acta Neuropathol. 89. 29-34 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami N,Ishiguro K,Ihara Y,Nonaka I, Sugita H,Imahori K: "Tau protein immunoreactivity in muscle fibers with rimmed vacuoles differs from that in regenerating muscle fibers" Acta Neuropathol. 90. 467-471 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 村上信行、竹光正和、倉繁隆信、埜中征哉: "神経筋疾患におけるrimmed vacuoleの意義 封入体筋炎とrimmed vacuoleを伴う遠位型ミオパチーの免疫組織学的比較検討を中心として" 臨床神経学. 34. 782-787 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami N,Ihara Y,Nonaka I: "Chloroquine treated rat : a possible model for Alzheimer's disease" Muscle Nerve. 18. 123-125 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami N,Goto Y,Itho M,Katsumi Y,wada T,Ozawa E,Nonaka I: "Sarcolemmal indetation in cardiomyopathy with metal retardation and vacuolar myopathy" Neuromusc Disord. 5. 149-155 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kiyomoto BH,Murakami N,Kishibayashi J,Sunohara N,Nonaka I: "Reducing bodies in distal myopathy with rimmed vacule formation" Acta Neuropathol. 89. 109-111 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami N,Ihara Y,Nonaka I: "Muscle fiber degeneration in distal myopathy with rimmed vacule formation" Acta Neuropathol. 89. 29-34 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murakami N,Ishiguro K,Ihara Y,Nonaka I,Sugita H,Imahori K.: "Tau protein immunoreactivity in muscle fibers with rimmed vacuoles differs from that in regenerating muscle fibers" Acta Neuropathol. 90. 467-471 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary

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Published: 1995-04-01   Modified: 2016-04-21  

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