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

我们建立了抗老年斑（SP）淀粉样蛋白的单克隆抗体，获得了一个克隆9D2，该克隆在阿尔茨海默病（AD）大脑中标记SP淀粉样蛋白原纤维，并与50/100 kDa多肽反应。我们纯化了9D2抗原并克隆了编码其前体的cDNA，该前体是一种在神经元中特异性表达的新型II型跨膜蛋白。该前体含有三个胶原样Gly-X-Y重复基序，提示我们将9D2抗原命名为CLAC（胶原样阿尔茨海默氏淀粉样斑块成分）及其前体CLAC-p （CLAC-前体）。CLAC- p的胞外结构域由furin convertase （sCLAC）分泌，并且在AD脑中CLAC的ammend被焦谷氨酸修饰。CLAC和CLAC- p特异性结合成纤维的Aβ，暗示CLAC/CLAC- p参与AD的β-淀粉样变和神经元变性。

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.