Single-molecule fluorescence imaging and deep learning reveal highly heterogeneous aggregation of amyloid-β 42

Abstract

Significance There are various diseases caused by protein aggregation such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. From the diversity in the fibril structure, aggregation is expected to occur via heterogeneous pathways. However, characterization of this heterogeneity is extremely difficult because it requires following individual fibril formation in a mixture from early oligomerization stages. In this work, we investigated aggregation of the 42-residue isoform of amyloid β (Aβ42) using single-molecule fluorescence imaging and deep learning. We could track the growth of individual fibrils, which allows for a quantitative description of heterogeneous fibril formation and discovery of a new fibril nucleation mechanism. Further characterization of heterogeneity involving Aβ42 will be important for better understanding the disease mechanism.