2002 Fiscal Year Final Research Report Summary
Development of diagnostic and therapeutic strategies for Alzheimer's disease : focus on a novel cerebral amyloid component
| Project/Area Number |
12558088
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | The University of Tokyo |
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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)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Alzheimer / collagen / amyloid / CLAC |
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| 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.
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