Real-Time Analysis of Specific Binding between Apolipoprotein E Isoforms and Amyloid β-Peptide by Dual Polarization Interferometry
Yu Wang, Yu Xue, Shuang Wang, Jianshe Huang, Xiurong Yang
Abstract
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 Aβ1–40. By evaluation of detailed binding information provided by DPI, the affinities between Apo E isoforms and Aβ1–40 follow the order of E4 > E3 > E2, and the dissociation constants (KD) of Aβ1–40 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.