Formation of dynamic soluble surfactant-induced amyloid ß peptide aggregation intermediates.

Intermediate amyloidogenic states along the amyloid ß peptide (Aß) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aß aggregation, we here investigate surfactant-induced Aß aggregation. This process leads to co-aggregates featuring a ß-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aß in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via ß-structure to the fully formed α-helical state at high surfactant concentration. The ß-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aß co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with ß-structure promoting substances, such as surfactants, Aß is kinetically driven toward an aggregation-prone state.