β淀粉样蛋白寡聚体（AβO）是诱发阿尔茨海默症（AD）的始动因素和关键标记物，是Aβ聚集进程的中间环节，其电学性质解析尚未见报道，Aβ聚集机制尚未完全阐明。我们前期研究发现不同Aβ聚集体之间存在介电差异，水分子运动是驱动AβO空间构象动态变化的关键因素。提示建立AβO电学性质、结构与聚集行为的关联，是阐释Aβ聚集机制的重要方向。本项目拟采用介电频谱技术、数学-物理模型解析和分子动力学模拟技术，在40Hz~20GHz宽频范围内，明确三种Aβ蛋白的介电异质性参数，评价抑制剂的抗聚集作用效果，解析不同浓度、温度、pH和时间等条件AβO的介电参数变化及其多种介电弛豫现象（如：离子渗透、偶极侧链取向极化和水分子极化），分析水分子运动与AβO空间构象变化的关系，建立介电性质-空间构象-聚集行为的关联。为Aβ聚集机制的阐释，AD的早期诊断、疾病监测、药物研发和治疗提供理论基础和新思路。

Amyloid β Oligomers (Aβ oligomers, AβO) is the key factor driving pathogenesis and biomarkers in Alzheimer’s Disease (AD), which is a middle link of the aggregation process. The electrical properties of AβO and the mechanism of Aβ aggregation have not been fully elucidated yet. In our previous study, we found that the various Aβ aggregates had dielectric characteristic difference, and the dynamic changes of the spatial conformation of AβO were driven by water molecular motion. It is suggested that establishing the correlation between AβO electrical characteristics, spatial conformation and the aggregation behavior may be an important direction to explain the mechanism of Aβ aggregation. This project intends to explore the dielectric properties and its aggregation mechanism of Aβ by Dielectric Spectroscopy (DS), Mathematical-Physical model analysis, and Molecular Dynamics (MD) simulation technology in a wide frequency range of 40 Hz~20 GHz. We will clarify the dielectric heterogeneity parameters of Aβ protein, evaluate the anti-aggregation effect of the inhibitors, and analyze the dielectric parameter changes and the various dielectrics relaxation phenomena (such as ion penetration, dipole side-chain orientation polarization, and water molecule polarization) of AβO under the external factors (concentration, temperature, pH and time). We also will explain the relation of water molecule motion to AβO spatial conformational changes, and establish a relationship between dielectric properties, protein structure and aggregation behavior. It provides theoretical basis and new ideas for the interpretation of Aβ aggregation mechanism, the early diagnosis, disease surveillance, drug development, and the treatment of AD.