TRANSTHYRETIN SEQUESTERS AMYLOID-BETA PROTEIN AND PREVENTS AMYLOID FORMATION
TRANSTHYRETIN SEQUESTERS AMYLOID-BETA PROTEIN AND PREVENTS AMYLOID FORMATION
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DOI：
10.1073/pnas.91.18.8368
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发表时间：
1994-08-30
影响因子：
11.1
通讯作者：
GOLDGABER, D
中科院分区：
文献类型：
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作者：
SCHWARZMAN, AL;GREGORI, L;GOLDGABER, D
阿尔茨海默病的主要病理特征是脑和脑血管中聚集的淀粉样β蛋白(Aβ)沉积。然而，在健康人和阿尔茨海默病患者的脑脊液中，Aβ以可溶形式被发现。我们假设Aβ的封闭可以阻止淀粉样蛋白的形成。未能隔离阿尔茨海默病中的Aβ可能导致淀粉样变性。当我们将Aβ添加到患者和对照组的脑脊液中时，它被迅速隔离成与转甲状腺素的稳定络合物。在脑脊液中没有观察到载脂蛋白E的复合体，它在体外被证明能与Aβ结合。另外，体外研究表明，提纯的转甲状腺素和载脂蛋白E都可以防止淀粉样蛋白的形成。
The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patients with Alzheimer disease. We postulate that sequestration of A beta precludes amyloid formation. Failure to sequester A beta in Alzheimer disease may result in amyloidosis. When we added A beta to cerebrospinal fluid of patients and controls it was rapidly sequestered into stable complexes with transthyretin. Complexes with apolipoprotein E, which has been shown to bind A beta in vitro, were not observed in cerebrospinal fluid. Additional in vitro studies showed that both purified transthyretin and apolipoprotein E prevent amyloid formation.