Shoji M, Golde T E, Ghiso J, Cheung T T, Estus S, Shaffer L M, Cai X D, McKay D M, Tintner R, Frangione B
Department of Neurology, Gunma University, Japan.
Science. 1992 Oct 2;258(5079):126-9. doi: 10.1126/science.1439760.
The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.
4千道尔顿（39至43个氨基酸）的β淀粉样蛋白（β-AP），它以淀粉样蛋白形式沉积在阿尔茨海默病患者的大脑中，来源于一种大蛋白，即β淀粉样蛋白前体（β-APP）。表达含β-AP的羧基末端β-APP衍生物的人单核白血病（K562）细胞释放出大量可溶性4千道尔顿β-APP衍生物，该衍生物与沉积在阿尔茨海默病中的β-AP基本相同。用表达全长β-APP的构建体转染的人神经母细胞瘤（M17）细胞和仅表达内源性β-APP的M17细胞也释放可溶性4千道尔顿β-AP，并且在阿尔茨海默病患者和正常个体的脑脊液中很容易检测到类似（如果不是相同）的片段。因此，细胞通常产生并释放可溶性4千道尔顿β-AP，它与以不溶性淀粉样纤维形式沉积在阿尔茨海默病中的4千道尔顿β-AP基本相同。
