In vitro electrochemical detection of the degradation of amyloid-p oligomers

The clearance of overloaded amyloid p (Ap) oligomers is thought to be an attractive and potential strategy for the therapy of Alzheimer's disease (AD). A variety of strategies have already been utilized to study Ap degradation in vitro. Here, the electrochemical detection based on direct electrooxidation of specific Tyr residues within Ap peptide has been developed as a simple and robust approach for monitoring the oli-gomers' degradation. C60 was employed for photodegrading Ap oligomers due to the generated ROS under light irradiation. The oxidation current of Tyr residues by square wave voltammetry (SWV) increased upon the Ap degradation, confirming that the structure variation of Ap peptide indeed influenced the exposure of those redox species to the electrode surface and final signal output. Chronoamperometric assay also found the electrooxidation of Tyr undergone an irreversible process. Additionally, the direct electrochemistry was capable of detecting the aggregation with rapid test and better sensitivity in com-pared with dynamic light scattering (DLS), atomic force microscopy (AFM) and thioflavin T (ThT) based fluorescence assay. Thus, this work indicated the potential application of direct electrochemistry in the in vitro measurement of Ap degradation and clearance, providing new insights and a complementary means into the AD theranostics. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study developed an electrochemical detection method for monitoring the degradation of amyloid p oligomers. By directly electrooxidizing specific tyrosine residues within the oligomers, the degradation level could be measured, confirming the influence of Ap peptide structure on signal output. The method also displayed better sensitivity compared to dynamic light scattering, atomic force microscopy, and fluorescence assays.