M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348, Kraków, Poland.
Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland.
Angew Chem Int Ed Engl. 2021 Feb 23;60(9):4545-4550. doi: 10.1002/anie.202010331. Epub 2021 Jan 7.
Abnormal aggregation of amyloid-β is a very complex and heterogeneous process. Owing to methodological limitations, the aggregation pathway is still not fully understood. Herein a new approach is presented in which the secondary structure of single amyloid-β aggregates is investigated with tip-enhanced Raman spectroscopy (TERS) in a liquid environment. Clearly resolved TERS signatures of the amide I and amide III bands enabled a detailed analysis of the molecular structure of single aggregates at each phase of the primary aggregation of amyloid-β and also of small species on the surface of fibrils attributed to secondary nucleation. Notably, a β-sheet rearrangement from antiparallel in protofibrils to parallel in fibrils is observed. This study allows better understanding of Alzheimer's disease etiology and the methodology can be applied in studies of other neurodegenerative disorders.
淀粉样蛋白-β的异常聚集是一个非常复杂和多样的过程。由于方法学的限制，聚集途径仍不完全清楚。在这里提出了一种新的方法，即在液相中使用尖端增强拉曼光谱（TERS）研究单淀粉样蛋白-β聚集体的二级结构。酰胺 I 和酰胺 III 带的明显分辨的 TERS 特征使得能够在淀粉样蛋白-β一级聚集的每个阶段以及纤维表面的归因于二级成核的小物种的单个聚集体的分子结构进行详细分析。值得注意的是，观察到原纤维中的反平行β-片层重排为纤维中的平行。这项研究有助于更好地理解阿尔茨海默病的病因，并且该方法可以应用于其他神经退行性疾病的研究。
