Spatial transmission of the Alzheimer’s amyloid beta peptide by secondary oligomers

The formation of amyloid fibrils from amyloid-beta peptides is a hallmark of Alzheimer’s disease. 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 via a diffusion mechanism involving soluble oligomeric species. These species, catalytically produced through secondary nucleation, significantly accelerate the propagation velocity of the reaction wavefront. Our findings suggest that, in addition to their potential role in toxicity, these soluble secondary oligomeric species are key drivers of the spatial spreading of aggregation and should therefore be considered primary targets for therapeutic intervention.