One of the pathogenesis hypotheses of Alzheimer’s disease (AD) is amyloid depositions and neurofibrillary tangles. Apolipoprotein E (Apo E) acts a vital part in the development of AD by affecting the aggregation and clearance of amyloid-β (Aβ). In this paper, a dual polarization interferometry (DPI) technique was employed for a real-time investigation toward the binding events of Apo E isoforms, for instance, Apo E2, Apo E3, and Apo E4, with Aβ_1–40. By evaluation of detailed binding information provided by DPI, the affinities between Apo E isoforms and Aβ_1–40 follow the order of E4 > E3 > E2, and the dissociation constants (K_D) of Aβ_1–40 with Apo E2, Apo E3, and Apo E4 were determined to be 251 ± 37, 40 ± 0.65, and 24.6 ± 2.42 nM, respectively. Our findings reveal the isoform-specific binding behaviors from a kinetics perspective, which can help us understand that Apo E4 has a higher risk of causing AD because of its promoting effect on Aβ aggregation and fibrillation and inefficient clearance of Aβ. Remarkably, this work provides a promising method for exploring the dynamics of interactions between biomolecules and expectantly contributes to the development of AD drugs and therapies targeting Apo E and Aβ.

中文翻译：

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双极化干涉法实时分析载脂蛋白E同工型与淀粉样β肽之间的特异性结合

阿尔茨海默氏病（AD）的发病机理假说之一是淀粉样蛋白沉积和神经原纤维缠结。载脂蛋白E（Apo E）通过影响淀粉样β（Aβ）的聚集和清除在AD的发展中起着至关重要的作用。在本文中，采用双极化干涉术（DPI）技术实时研究Apo E亚型的结合事件，例如Apo E2，Apo E3和Apo E4与_Aβ1–40的结合事件。通过由DPI提供了详细的绑定信息的评价，载脂蛋白E基因同种型和Aβ之间的亲和_1-40按照E4> E3> E2的顺序，和所述解离常数（ķ _d Aβ的）_1-40用Apo E2，Apo E3和Apo E4分别测得的浓度分别为251±37、40±0.65和24.6±2.42 nM。我们的发现从动力学的角度揭示了同工型特异性的结合行为，这可以帮助我们理解Apo E4由于其对Aβ聚集和原纤化的促进作用以及Aβ的清除效率低而具有引起AD的较高风险。值得注意的是，这项工作为探索生物分子之间相互作用的动力学提供了一种有前途的方法，有望为开发针对Apo E和Aβ的AD药物和疗法做出贡献。