Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
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发表时间：
1994-11
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通讯作者：
Thomas;Wisniewski;E. M. Castaño;A. Golabek;T. Vogel;B. Frangione
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作者：
Thomas;Wisniewski;E. M. Castaño;A. Golabek;T. Vogel;B. Frangione
许多研究已经建立了载脂蛋白（apo）E4等位基因和迟发性阿尔茨海默病之间的联系。目前尚不清楚载脂蛋白E是否在阿尔茨海默病的发病机制中起直接作用，以及它与淀粉样蛋白β（A β）和tau蛋白的重要相互作用（如果有的话）是什么。载脂蛋白E在所有类型的淀粉样蛋白沉积物中均被发现，并且已从淀粉样蛋白中分离出载脂蛋白E片段。此外，载脂蛋白E已显示结合可溶性A β。已经提出apo E起促进和/或调节A β原纤维形成的作用。已经确定，与A β同源的肽在溶液中会形成淀粉样原纤维。通过使用电子显微镜和用于原纤维形成的硫磺素T测定，我们发现apo E和apo E4在所使用的体外条件下特别增强A β肽的这种自发原纤维形成。这些体外数据表明，载脂蛋白E4亚型是阿尔茨海默病的一个危险因素，它可以加速在其缺失时可能发生的过程。
Numerous studies have established a linkage between the apolipoprotein (apo) E4 allele and late-onset Alzheimer's disease. It remains unclear if apo E plays a direct role in the pathogenesis of Alzheimer's disease and what, if any, are its significant interactions with amyloid beta (A beta) and tau. Apo E has been found immunohistochemically in all types of amyloid deposits and apo E fragments have been isolated from amyloid. Furthermore, apo E has been shown to bind soluble A beta. It has been proposed that apo E acts to promote and/or modulate A beta fibril formation. It is well established that peptides homologous to A beta will form amyloid-like fibrils in solution. With the use of electron microscopy and a thioflavin T assay for fibril formation we found that apo E and apo E4 in particular enhance this spontaneous fibrillogenesis of A beta peptides under the in vitro conditions used. These in vitro data suggest that the apo E4 isoform is a risk factor for Alzheimer's disease that acts to accelerate a process that can occur in its absence.