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Role of beta protein and cystatin C in the cerebral amyloid angiopathy

Research Project

Project/Area Number 06670193
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionYamaguchi University

Principal Investigator

ISHIHARA Tokuhiro  Yamaguchi Univ.Sch.of Med.Professor, 医学部, 教授 (70089910)

Co-Investigator(Kenkyū-buntansha) HOSHII Yoshinobu  Yamaguchi Univ.Sch.of Med.Assistant Professor, 医学部, 助手 (00263773)
TAKAHASHI Mutsuo  Yamaguchi Univ.Sch.of Med.Associate Professor, 医学部, 助教授 (50112230)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsAmyloid / Angiopathy / Cerebral vessel / beta Protein / Cystatin C / Apolipoprotein E / Immunohistochemistry / Immunoelectron microscopy / アミイロイド
Research Abstract

Cerebral amyloid angiopathy (CAA) in the elderly, designated by the deposition of beta protein, has been thought as a cause of cerebral hemorrhage. We have reported that CAA is the most common cause of superficial cerebral hemorrhage in patients older than 60 years. However, the mechanism for the rupture of amyloid-laden vessels remains unclear. We have revealed that CAA seen in some sporadic aged individuals can show a immunohistochemical reactivity towards antibodies to both beta protein and cystatin C (Cys C), and that Cys C was not actually an integral component of cerebrovascular amyloid fibrils in these cases. Immunohistochemical studies were carried out on biopsy specimens from 29 patients with cerebral subcortical hemorrhage using primary antibodies against beta protein, Cys C,and apolipoprotein E (Apo E). Cerebral vessels in all cases were reactive for anti-beta protein and Apo E antibodies, and in 26 (89.7%) out of 29 cases showed positive immunoreactivity for Cys C.beta Protein and Apo E immunoreactivities were demonstrated predominantly in the media and adventitia of a small artery. Serial sections immunostained for Cys C showed an intense labelling of the adventitia of vessel wall. On electron microscopy, amyloid fibrils, measuring 10 nm in width, were located mainly in the tunica media of the arteries, and in less involved vessels they tended to be situated among the collagen fibers in the adventitia and smooth muscle cells in the outer zone of the media. On immunoelectron microscopy for beta protein, all of the amyloid fibrils in the vascular walls were specifically labelled by gold particles. The present study indicates that Cys C superimposed beta protein amyloid in CAA plays an important role for the rupture of amyloid-laden vessels.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Y. Hoshii et al.: "Immunohistochemical classification of 140 autopsy cases with systemic amyloidosis." Pathol Int. 44. 352-358 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 石原得博他: "代謝性疾患の診断における電子顕微鏡の役割(II)" 電子顕微鏡. 29. 130-136 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Ishihara et al.: "Characteristic ultrastructural findings in metabolic and storage diseases." Bull Yamaguchi Med Sch. 41. 113-142 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 石原得博他: "厚生省特定疾患『アミロイドーシス』-その総説と発生病理に関して-" 山口医学. 44. 297-318 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Iwata、et al.: "Hepatic amyloidosis in Japan : Histological and morphometric analysis based on amyloid proteins." Hum Pathol. 26. 1148-1153 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 石原得博他: "脳アミロイドアンギオパチー生検例の免疫 組織化学的検討(出血群と非出血群の比較)" 厚生省特定疾患アミロイドーシス 調査研究班1994年度研究報告書. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Hoshii, T.Ishihara, et al.: "Immunohistochemical classification of 140 autopsy cases with systemic amyloidosis." Pathol Int. 44. 352-358 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Mihara, T.Ishihara, et al.: "Intervertebral disc amyloidosis : histochemical and ultrastructural observations." Histopathology. 25. 415-420 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Kawamura, T.Ishihara, et al.: "Incidence and distribution of isolated atrial amyloid : Histologic and immunohistochemical studies of 100 aging hearts." Pathol Int. 45. 335-342 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Ishihara, M.Takahashi: "Electron microscopic diagnosis in metabolic diseases (II). (in Japanese)" Electron-Microscopy. 29. 130-136 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Ishihara, et al.: "Characteristic ultrastructual findings in metabolic and storage diseases." Bull Yamaguchi Med Sch. 41. 113-142 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Ishihara, et al.: "Amyloidosis designated as intractable disease by the Ministry Health and Welfare of Japan -A review and its pathogenesis- (in Japanese)" Yamaguchi Med J. 44. 297-318 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Iwata, T.Ishihara, et al.: "Hepatic amyloidosis in Japan : Histological and morphometric analysis based on amyloid proteins." Hum Pathol. 26. 1148-1153 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishihara, et al.: "Immunohistochemical study of biopsy specimens in amyloid angiopathy -Comparison between cases with and without cerebral hemorrhage- (in Japanese)" Annual Rep of Amyloidosis Res Committee, Ministry of Health and Welfare of Japan. (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 石原得博: "厚生省特定疾患「アミロイドーシス」-その総論と発症機序に関して-" 山口医学. 44. 297-318 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 石原得博: "脳アミロイドアンギオパチー生検例の免疫組織化学的検討" 厚生省特定疾患アミロイドーシス調査研究班1995年度報告書. (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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