Soto C, Golabek A, Wisniewski T, Castaño E M
Department of Neurology, New York University Medical Center, NY 10016, USA.
Neuroreport. 1996 Feb 29;7(3):721-5. doi: 10.1097/00001756-199602290-00010.
Amyloid beta-peptide (A beta) is a major component of neuritic plaques, a feature of Alzheimer's disease (AD) brains. Recently, we showed that A beta adopts two major conformational states in solution, which differ in their abilities to form amyloid. These are highly amyloidogenic conformer (A beta ac) with a high content of beta-sheet and a slowly amyloidogenic conformer (A beta nac) with a random coil conformation. Apolipoprotein E (apoE), particularly the E4 isoform, which is genetically associated with AD, binds to A beta and modulates fibrillogenesis in vitro. In the present work, the influence of apoE on the conformation of A beta peptides was studied. The results suggest that, under the conditions used, apoE enhances amyloid formation by inducing the conformational transition from A beta nac into A beta ac. We propose that an important step in A beta fibrillogenesis is the transformation induced by apoE of the soluble non-amyloidogenic into the pathological amyloidogenic conformer of A beta.
β-淀粉样肽（Aβ）是神经炎性斑块的主要成分，是阿尔茨海默病（AD）大脑的一个特征。最近，我们发现Aβ在溶液中呈现两种主要构象状态，它们形成淀粉样蛋白的能力不同。一种是具有高β-折叠含量的高度淀粉样生成构象体（Aβac），另一种是具有无规卷曲构象的缓慢淀粉样生成构象体（Aβnac）。载脂蛋白E（apoE），特别是与AD有遗传关联的E4亚型，可与Aβ结合并在体外调节纤维形成。在本研究中，研究了apoE对Aβ肽构象的影响。结果表明，在所使用的条件下，apoE通过诱导Aβnac向Aβac的构象转变来增强淀粉样蛋白的形成。我们提出，Aβ纤维形成中的一个重要步骤是apoE诱导的Aβ从可溶性非淀粉样生成构象向病理性淀粉样生成构象的转变。
