Aggregation of amyloid-β peptide (Aβ) is hypothesized to be the primary cause of Alzheimer's disease (AD) progression. Aβ aggregation has been widely studied using conventional sensing tools like emission fluorescence, electron microscopy, mass spectroscopy, and circular dichroism. However, none of these techniques can provide cost-efficient, highly sensitive quantification of Aβ aggregation kinetics at the molecular level. Among the influences on Aβ aggregation of interest to disease progression is the acceleration of Aβ aggregation by acetylcholinesterase (AChE), which is present in the brain and inflicts the fast progression of disease due to its direct interaction with Aβ. In this work, we demonstrate the ability of a biological nanopore to map and quantify AChE accelerated aggregation of Aβ monomers to mixed oligomers and small soluble aggregates with single-molecule precision. This method will allow future work on testing direct and indirect effects of therapeutic drugs on AChE accelerated Aβ aggregation as well as disease prognosis.

β 淀粉样肽 (Aβ) 的聚集被认为是阿尔茨海默病 (AD) 进展的主要原因。Aβ 聚集已使用发射荧光、电子显微镜、质谱和圆二色性等传统传感工具进行了广泛研究。然而，这些技术都无法在分子水平上提供经济高效、高灵敏度的 Aβ 聚集动力学定量。Aβ 聚集对疾病进展的影响之一是乙酰胆碱酯酶 (AChE) 加速 Aβ 聚集，AChE 存在于大脑中，由于与 Aβ 直接相互作用，导致疾病快速进展。在这项工作中，我们展示了生物纳米孔能够以单分子精度绘制和量化 AChE 加速 Aβ 单体向混合低聚物和小可溶性聚集体的聚集。该方法将允许未来测试治疗药物对 AChE 加速 Aβ 聚集以及疾病预后的直接和间接影响。