Figure 4. Schematic illustration of the reaction pathways of oligomers during amyloid aggregation and the associated reaction rates determined in this work for Aβ42.

Amyloid fibril proliferation occurs through a two-step nucleation mechanism involving oligomer formation followed by oligomer conversion into fibrillar structures. The heterogeneous ensemble of oligomers includes not only converting species but consists mainly of unstable oligomers that can dissociate back to monomers. Oligomers undergo repeated cycles of formation-dissociation before eventually converting into species that are able to grow into new fibrils. The reaction rates are shown here for Aβ42 at a concentration of 5 μM (rate constants in Supplementary Sec. 6.3) and are to be interpreted as averages over the heterogeneous ensemble of oligomers. The geometric mean of the rates of oligomer formation, oligomer conversion and fibril elongation (which constitute the autocatalytic cycle of fibril self-replication, Supplementary Sec. 5.3) yields the characteristic rate of amyloid fibril formation (Supplementary Sec. 6.5 and Supplementary Fig. 17).