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  • The EMBO Journal (2002) 21, 1524 - 1534
  • doi:10.1093/emboj/21.7.1524

CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV

Tadafumi Hashimoto1,8, Tomoko Wakabayashi1,8, Atsushi Watanabe2,3, Hisatomo Kowa1,4, Ritsuko Hosoda1,5, Atsushi Nakamura6, Ichiro Kanazawa4, Takao Arai5, Koji Takio2, David M.A. Mann7 and Takeshi Iwatsubo1

  1. Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan
  2. Biomolecular Characterization Division, Characterization Center, RIKEN, Wako 351-0198, Japan
  3. Present address: National Institute for Longevity Science, Obu 474-8522, Japan
  4. Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
  5. Faculty of Science and Technology, Science University of Tokyo, Noda, Japan
  6. Taisho Pharmaceutical Co. Ltd, Omiya, Saitama 330-8530, Japan
  7. Greater Manchester Neurosciences Centre, Hope Hospital, Salford M6 8HD, UK
  8. T.Hashimoto and T.Wakabayashi contributed equally to this work

Correspondence to:

Takeshi Iwatsubo, E-mail: iwatsubo@mol.f.u-tokyo.ac.jp

Received 10 January 2002; Accepted 8 February 2002; Revised 8 February 2002

We raised monoclonal antibodies against senile plaque (SP) amyloid and obtained a clone 9D2, which labeled amyloid fibrils in SPs and reacted with approx50/100 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 and was partially homologous to collagen type XIII. Thus, we named the 9D2 antigen as CLAC (collagen-like Alzheimer amyloid plaque component), and its precursor as CLAC-P/collagen type XXV. The extracellular domain of CLAC-P/collagen type XXV was secreted by furin convertase, and the N-terminus of CLAC deposited in AD brains was pyroglutamate modified. Both secreted and membrane-tethered forms of CLAC-P/collagen type XXV specifically bound to fibrillized Abeta, implicating these proteins in beta-amyloidogenesis and neuronal degeneration in AD.

  • Keywords:

    • Alzheimer's disease,
    • amyloid,
    • collagen