Cai X D, Golde T E, Younkin S G
Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106.
Science. 1993 Jan 22;259(5094):514-6. doi: 10.1126/science.8424174.
The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta.
在阿尔茨海默病（AD）中形成纤维状沉积物的4千道尔顿β淀粉样蛋白（Aβ），来源于一种被称为β淀粉样蛋白前体（βAPP）的大型蛋白质。对转染了表达野生型βAPP或与家族性AD相关的突变体βAPPδNL构建体的人神经母细胞瘤（M17）细胞进行了比较。连续代谢标记8小时后，表达βAPPδNL的细胞中一种带有Aβ的羧基末端βAPP衍生物比表达野生型βAPP的细胞多五倍，并且它们向培养基中释放的Aβ多六倍。因此，这种突变型βAPP可能导致AD，因为其加工过程发生改变，从而释放出更多量的Aβ。
