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2002 Fiscal Year Final Research Report Summary

Development of diagnostic and therapeutic strategies for Alzheimer's disease : focus on a novel cerebral amyloid component

Research Project

Project/Area Number 12558088
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Nerve anatomy/Neuropathology
Research InstitutionThe University of Tokyo

Principal Investigator

IWATSUBO Takeshi  Professor, Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 大学院・薬学系研究科, 教授 (50223409)

Co-Investigator(Kenkyū-buntansha) NISHIZAWA Yukio  Chief(Researcher), Biology Unit, Department of Drug Discovery, Eisai Co., 基礎研究本部・バイオロジーユニット, ユニット長(研究職)
TOMITA Taisuke  Research Associate, Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 大学院・薬学系研究科, 助手 (30292957)
Project Period (FY) 2000 – 2002
KeywordsAlzheimer / collagen / amyloid / CLAC
Research Abstract

We raised monoclonal antibodies against senile plaque (SP) amyloid and obtained a clone 9D2, which labeled amyloid fibrils in SP and reacted with 50/100 kDa polypeptides in Alzheimer's disease (AD) brains. We purified the 9D2 antigens and cloned a cDNA encoding its precursor, which was a novel type II transmembrane protein specifically expressed in neurons. This precursor harbored three collagen-like Gly-X-Y repeat motifs, prompting us to designate 9D2 antigen CLAC (collagen-like Alzheimer amyloid plaque component), and its precursor CLAC-P (CLAC-precursor). The extracellular domain of CLAC-P was secreted by furin convertase (sCLAC), and the ammo terminus of CLAC in AD brains was pyroglutamate-modified. sCLAC and CLAC-P specifically bound to fibrillized Aβ, implicating CLAC/CLAC-P in β- amyloidogenesis and neuronal degeneration in AD.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Hashimoto T: "CLAC : a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV"EMBO J. 21. 1524-1534 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomita T: "Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments"FEBS lett. 520. 117-121 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takasugi N: "The mechanism of γ-secretase activities through high molecular weight complex formation of presenilins is conserved in Drosophila melanogaster and mammals"J Biol Chem. 277. 50198-50205 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto T: "CLAC : a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV"EMBO J. 21. 1524-1534 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomita T: "Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments"FEBS lett. 520. 117-121 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takasugi N: "The mechanism of γ-secretase activities through high molecular weight complex formation of presenilins is conserved in Drosophila melanogaster and mammals"J Biol Chem. 277. 50198-50205 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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