Application of electrochemical method to a comparative study of spontaneous aggregation of amyloid-β isoforms

The tyrosine based electrochemical analysis of spontaneous aggregation of amyloid-β peptides, Aβ42 and its phosphorylated and isomerized forms, pS8-Aβ42 and isoD7-Aβ42, implicated in the Alzheimer's disease pathogenesis, was carried out by square wave voltammetry (SWV) on carbon screen printed electrodes (SPE). The Aβ oxidation signal was shown to be generated by peptide molecules constituting the ‘soluble’ (sedimentation-resistant) fraction in the course of spontaneous Aβ aggregation under in vitro conditions. It has been found for the first time that oxidation currents for Aβ42, pS8-Aβ42, and isoD7-Aβ42 peptides decrease at a close rate in the course of their spontaneous aggregation. That suggests that these Aβ isoforms have similar ability to aggregate. Consequently, a distinct aggregation behavior observed for Aβ isoforms studied with methods detecting the occurrence of aggregates (turbidimetry and dynamic light scattering) or evaluating the aggregate structure (thioflavin T based fluorescence assay) may be completely attributed to differences in size and structure of aggregates formed. The work emphasizes the utility of cost-effective and rapid electrochemical techniques such as SWV on carbon SPE for in vitro studies of the aggregation of Aβ peptides with pathologically meaningful post-translational modifications. [Display omitted] •The Aβ oxidation signal is generated by mono- and oligomeric molecules from the ‘soluble’ fraction.•During aggregation, oxidation peaks for Aβ42, pS8-Aβ42, and isoD7-Aβ42 decrease at a close rate.•Aβ42, pS8-Aβ42, and isoD7-Aβ42 isoforms have similar ability to aggregate.•Aβ42, pS8-Aβ42, and isoD7-Aβ42 are different in size and structure of aggregates formed.