Misfolding and aggregation of amyloidogenic proteins is associated with a vast number of neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), termed protein aggregation diseases12. Numerous studies have shown that amyloidogenic proteins are capable of spontaneous assembly into aggregates and eventually form fibrillar structures found in amyloid or amyloid-like deposits34. These studies have led to the amyloid cascade hypothesis, which posits that the disease onset involves a spontaneous assembly of amyloidogenic polypeptide, and that the accumulation of aggregates defines the disease state567. Numerous studies support this hypothesis that currently is considered the main model for the onset of AD, PD, HD, and other diseases. Although the amyloid cascade hypothesis cannot explain all facts related to the development of these diseases, it remains the major underlying hypothesis of in vitro and in vivo studies related to the molecular mechanisms of amyloid aggregation causing neurodegenerative diseases8. A strong support for the amyloid cascade hypothesis comes from recent studies that demonstrated that antibody-based immunotherapy against Aβ improved cognition in a dose-dependent manner9. Evidence of similarities of structural features of aggregates extracted from amyloid plaques with those of Aβ aggregates assembled in vitro provide additional support for the use of in vitro Aβ aggregation studies for understanding Aβ structural dynamics in vivo10. Amyloid aggregates can be visualized by electron microscopy and atomic force microscope (AFM) (e.g. refs 11 and 12 and references therein), and structural techniques including X-ray and NMR applied to fibrils have revealed a highly ordered arrangement of protein monomers13. However, recent studies have led to the discovery that oligomers rather than fibrils are neurotoxic31415. Studies of these transient oligomeric species have been enabled by the development of novel approaches1617 and have shown that at the very early aggregation stage, unstructured monomers form stable dimers due to structural transitions of monomers. In turn, these results suggest that the lack of structure in monomers can facilitate the aggregation. However, there is a serious complication with translating current knowledge on amyloid aggregation in vitro to understand the aggregation process in vivo —namely, the concentrations of amyloidogenic polypeptides are dramatically different in vivo versus in vitro. For example, whereas the critical concentration for the spontaneous aggregation of Aβ peptide in vitro is in the micromolar range, physiological concentrations of Aβ are in the low nanomolar range1819. At such low concentrations, Aβ aggregation cannot occur in vitro. Intracellular crowding effects18 can facilitate the aggregation process, but these do not solve the problem. Recently, we have found that dimers of α-synuclein (α-Syn) could be assembled at nanomolar concentrations, if the target monomer is tethered to a surface20. These data led us to hypothesize that binding to the surface can be a factor dramatically facilitating the aggregation process. This hypothesis is supported by recent studies in which the assembly of large α-Syn aggregates on a glass surface was observed with the protein concentration in the nanomolar range21.