Different Aggregation Pathways and Structures for Aβ40 and Aβ42 Peptides

Self-aggregation of amyloid-beta (A beta) peptides has been known to play a vital role in the onset stage of neurodegenerative diseases, indicating the necessity of understanding the aggregation process of A beta peptides. Despite previous studies on the aggregation process of A beta peptides, the aggregation pathways of A beta isoforms (i.e., A beta 40 and A beta 42) and their related structures have not been fully understood yet. Here, we study the aggregation pathways of A beta 40 and A beta 42, and the structures of A beta 40 and A beta 42 aggregates during the process, based on fluorescence and atomic force microscopy (AFM) experiments. It is shown that in the beginning of aggregation process for both A beta 40 and A beta 42, a number of particles (i.e., spherical oligomers) are formed. These particles are subsequently self-assembled together, resulting in the formation of different shapes of amyloid fibrils. Our finding suggests that the different aggregation pathways of A beta isoforms lead to the amyloid fibrils with contrasting structure.

Automated summary

The study found that in the initial stage of aggregation process for both Aβ40 and Aβ42, multiple particles are formed which later self-assemble to form amyloid fibrils of different shapes. Different aggregation pathways of Aβ isoforms lead to amyloid fibrils with contrasting structures.