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Inhibitory effects of apolipoprotein E on Alzheimer's beta-amyloid fibril formation in vitro.

Research Project

Project/Area Number 08670242
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionFukui Medical University

Principal Investigator

NAIKI Hironobu  Fukui Medical Univ., Fac.of Medicine Associate Prof., 医学部, 助教授 (10227704)

Co-Investigator(Kenkyū-buntansha) NAKAKUKI Kazuya  Fukui Medical Univ., Fac.of Medicine Professor, 医学部, 教授 (90024629)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsAlzheimer's disease / beta-amyloid fibril / apolipoprotein E / nucleation-dependent polymerization model / first-order kinetic model / spectrofluorometry / thioflavin T / βアミロイド線維 / チオフラビン T
Research Abstract

Recently, many research groups have examined the effect of apolipoprotein E (apoE) on beta-amyloid fibril (betaAf) formation in vitro. However, their data were somewhat controversial and no exact kinetic assessment of the role of apoE has thus far been available. We examined the effect of human apoE on betaAf formation in vitro, starting with various concentrations of freshly-prepared beta-amyloid (1-40) (beta1-40) and using fluorescence spectroscopy with thioflavine T.When 50 muM of beta-1-40 was incubated with an 1 : 1000 to 1 : 100 molar ratio of apoE,a dose dependent inhibitory effect of apoE was observed. Both the nucleation and extension phases of betaAf formation in vitro were inhibited by apoE.On the other hand, when 300 muM of beta1-40 was incubated with an 1 : 100 molar ratio of apoE,the inhibitory effect of apoE was completely abolished. We then focused our study on the kinetics of the inhibitory effect of apoE on the extension phase of betaAf formation in vitro, utilizing the recently established first-order kinetic model of betaAf extension in vitro [Naiki, H., & Nakakuki, K.(1996) Lab.Invest.74,374-383]. The mathematical treatment of the data suggests that apoE inhibits the extension of betaAf in vitro, by making a complex with beta1-40, thus eliminating free beta1-40 from the reaction mixture. The equilibrium association constant with beta1-40 was practically the same among the three major recombinant apoE isoforms. These results indicate that the effects of apoE on betaAf formation in vitro is differential, and could settle some of the controversy about beta-amyloid-apoE interaction in vitro.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Hironobu: "Concentration-dependent inhibitory effects of apolipoprotein E on Alzheimers β-amyloid fibril formation in vitro" Biochemistry. 36. 6243-6250 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naiki, H., et al.: "Concentration-dependent inhibitory effects of apolipoprotein E on Alzheimer's beta-amyloid fibril formation in vitro" Biochemistry. 36-20. 6243-6250 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hironobu Naiki: "Concentration-dependent innibitory effects of apolipoprotein E on Alzheimer's β-amyloid fibril formation in vitro" Bio chemistry. 36・20. 6243-6250 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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