Tsuzuki K, Fukatsu R, Takamaru Y, Yoshida T, Hayashi Y, Yamaguchi H, Fujii N, Takahata N
Department of Microbiology, Sapporo Medical University, Japan.
Neurosci Lett. 1995 Dec 29;202(1-2):77-80. doi: 10.1016/0304-3940(95)12205-2.
Previous immunohistochemical studies from this laboratory demonstrated that monoclonal antibodies raised against various regions of amyloid precursor protein (APP) (i.e., N-terminus, amyloid beta protein (A beta), and C-terminus) strongly labeled vacuoles in chloroquine-induced myopathy-affected muscle in rats. In this study, we used antibodies end specific for the A beta 40 and A beta 42 species, and a monoclonal antibody to A beta 1-9 which reacts with APP and A beta. Most vacuoles clearly reacted with anti-A beta 1-9, while about half reacted with anti-A beta 42, and only a few reacted with anti-A beta 40. These results demonstrate that vacuoles in chloroquine-induced myopathy-affected muscle contain cleaved A beta, and that distribution of the two major A beta species is similar to what is observed in A beta deposition in Alzheimer's disease (AD)-affected brain. This provides further evidence that chloroquine-induced myopathy in rats provides a suitable model to understand APP processing into A beta, and the role of APP in terms of the pathogenesis of AD.
该实验室先前的免疫组织化学研究表明，针对淀粉样前体蛋白（APP）不同区域（即N端、β淀粉样蛋白（Aβ）和C端）产生的单克隆抗体，能强烈标记氯喹诱导的大鼠肌病受累肌肉中的空泡。在本研究中，我们使用了对Aβ40和Aβ42亚型具有特异性的抗体，以及一种与APP和Aβ反应的抗Aβ1-9单克隆抗体。大多数空泡与抗Aβ1-9明显反应，约一半与抗Aβ42反应，只有少数与抗Aβ40反应。这些结果表明，氯喹诱导的肌病受累肌肉中的空泡含有裂解的Aβ，并且这两种主要Aβ亚型的分布与在阿尔茨海默病（AD）受累大脑中Aβ沉积中观察到的情况相似。这进一步证明，大鼠氯喹诱导的肌病为理解APP加工成Aβ以及APP在AD发病机制中的作用提供了一个合适的模型。
