The formation of amyloid deposits in human tissues is a defining feature of more than 50 medical disorders, including Alzheimer’s disease. Strong genetic and histological evidence links these conditions to the process of protein aggregation, yet it has remained challenging to identify a definitive connection between aggregation and pathogenicity. Using time-resolved fluorescence microscopy of individual synthetic vesicles, we show for the Aβ42 peptide implicated in Alzheimer’s disease that the disruption of lipid bilayers correlates linearly with the time course of the levels of transient oligomers generated through secondary nucleation. These findings indicate a specific role of oligomers generated through the catalytic action of fibrillar species during the protein aggregation process in driving deleterious biological function and establish a direct causative connection between amyloid formation and its pathological effects.

人体组织中淀粉样蛋白沉积物的形成是包括阿尔茨海默氏病在内的50多种医学疾病的定义特征。强有力的遗传学和组织学证据将这些条件与蛋白质聚集过程联系在一起，然而，要确定聚集与致病性之间的明确联系仍然具有挑战性。使用单个合成囊泡的时间分辨荧光显微镜，我们发现与阿尔茨海默氏病有关的Aβ42肽脂双层的破坏与通过次级成核产生的瞬时低聚物水平的时间过程线性相关。