Quantitative Aspects of Electrochemical Detection of Amyloid-β Aggregation

The tyrosine based electrochemical analysis of synthetic amyloid-beta (A beta) peptide - an analog of natural peptide implicated in Alzheimer's disease pathogenesis - was applied for a quantitative estimation of peptide aggregation in vitro. The analysis was carried out by square wave voltammetry (SWV) on carbon screen printed electrodes (SPE). The electrooxidation peak current (I-p) for A beta 42 peptide in different aggregation states was directly compared with the size and structure of A beta 42 aggregates occurring in the analyzed sample. Dynamic light scattering (DLS) and thioflavin T (ThT) based fluorescence assay were employed to estimate the size and structure of A beta 42 aggregates. The I-p was found to decrease in a linear fashion when the average diameter of aggregates and the relative ThT fluorescence in A beta 42 solutions exceeded 35 nm and 3, respectively, while being nearly constant below these values. It was suggested that the electrooxidation current is mostly generated by peptide monomers and that a depletion of the monomer pool due to inclusion of A beta 42 molecules in aggregates is responsible for the decrease of electrooxidation current. The direct electrochemistry is emerging as a method complementary to methods based on aggregates Q detection and commonly employed for monitoring Ab aggregation. The work further enlarges the basis for application of the cost-effective and rapid electrochemical techniques, such as SWV on carbon SPE, to in vitro studies of A beta aggregation.