Ma J, Yee A, Brewer H B, Das S, Potter H
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Nature. 1994 Nov 3;372(6501):92-4. doi: 10.1038/372092a0.
The protease inhibitor alpha 1-antichymotrypsin and the lipid transport protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid beta-peptide (A beta) in the filamentous amyloid deposits of Alzheimer's disease. We report here that these two amyloid-associated proteins serve a strong stimulatory role in the polymerization of A beta into amyloid filaments. Addition of either alpha 1-anti-chymotrypsin or apoE to the A beta peptide promoted a 10- to 20-fold increase in filament formation, with apoE-4, the isoform recently linked to the development of late-onset Alzheimer's disease, showing the highest catalytic activity. These and other experiments suggest that Alzheimer amyloid deposits arise when A beta is induced to form filaments by amyloid-promoting factors (pathological chaperones) expressed in certain brain regions.
蛋白酶抑制剂α1-抗糜蛋白酶和脂质转运蛋白载脂蛋白E（apoE）与阿尔茨海默病丝状淀粉样沉积物中的42个氨基酸的β肽（Aβ）密切相关。我们在此报告，这两种与淀粉样蛋白相关的蛋白质在Aβ聚合成淀粉样纤维的过程中发挥了强大的刺激作用。向Aβ肽中添加α1-抗糜蛋白酶或apoE可使纤维形成增加10至20倍，最近与晚发性阿尔茨海默病发展相关的异构体apoE-4显示出最高的催化活性。这些以及其他实验表明，当Aβ被某些脑区表达的淀粉样蛋白促进因子（病理性伴侣蛋白）诱导形成纤维时，就会出现阿尔茨海默病淀粉样沉积物。
