In the present study, we developed an approach enabling us to directly test our hypothesis. We utilized AFM to image assembly of aggregates on surfaces and compare this effect with their assembly in the bulk solution. We used full-length Aβ protein (Aβ-42), its aggregation-prone segment Aβ(14-23) peptide and the full-size α-Syn. The experiments demonstrate that all these proteins on mica surface assemble into aggregates at nanomolar concentration with essentially no aggregation propensity in the bulk solution. Time-lapse AFM imaging experiments in solution demonstrate that assembled aggregates can be released to the solution to act as seeds for the aggregation in bulk solution. Computational modeling allowed us to reveal the mechanism of the accelerated on-surface aggregation process. Given that the on-surface aggregates are oligomeric in nature, which are known to be the most neurotoxic species, we hypothesize that prevention of the on-surface aggregation should block the disease-prone process and can be considered a means for the development of future preventions and treatments for Alzheimer’s and similar neurodegenerative protein aggregation diseases.