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

Abstract

We raised monoclonal antibodies against senile plaque (SP) amyloid and obtained a clone 9D2, which labeled amyloid fibrils in SPs 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 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 Aβ, implicating these proteins in β‐amyloidogenesis and neuronal degeneration in AD.