Oligomers mediate the spatial transmission of Aβ peptide aggregation

Alzheimer’s disease (AD) is marked by the abnormal aggregation of amyloid-beta peptides within the central nervous system. The formation of amyloid fibrils from amyloid-beta peptides is a hallmark of AD Here, we demonstrate that the aggregation of amyloid-beta 42 spreads both spatially and temporally. By measuring the spatial propagation of amyloid-beta in macroscopic capillaries and performing Monte Carlo simulations, we show that this spreading occurs through a diffusion mechanism involving oligomers in solution. These species, catalytically produced through spontaneous secondary nucleation, significantly accelerate the propagation velocity of the reaction wavefront. Our findings suggest that, in addition to their potential role in toxicity, these oligomers in solution are key drivers of the spatial spreading of aggregation and can therefore be considered key targets for therapeutic intervention. Amyloid fibril formation from amyloid-beta peptides is a key feature of Alzheimer’s disease, yet the mechanisms of its spatial and temporal spread remain unclear. Here, the authors reveal that amyloid-beta 42 aggregation propagates via diffusion of oligomers in solution, highlighting these species as key drivers of the spatial spreading of aggregation.