Label-free electrochemical detection of Amyloid beta aggregation in the presence of iron, copper and zinc

Abstract

Aggregation of Amyloid-β (Aβ) peptides has been implicated in the progression of Alzheimer’s disease (AD). Although there is an underlying importance to determine the mechanism of aggregation in order to gain a better understanding of Aβ’s cytotoxicity, the exact pathway of aggregation is still unknown. As AD involves complicated neurodegenerative processes, many biological factors can implicate a role in the disease’s development. An area of interest is the marked increase in redox active metals (i.e. Fe, Cu, Zn). Metal-induced Aβ aggregates favor the production of reactive oxygen species (ROS), which induces more damage to cells inside the brain. Using square-wave voltammetry (SWV) to monitor tyrosine (Tyr) oxidation signal, early aggregation kinetics of Aβ in the presence and absence of metals has been observed in this report. Furthermore, a comparison was done between the full length Aβ42 and a truncated 16 amino-acid Aβ fragment (Aβ16) to determine the influence of the metal chelating histidine-rich region as well as the hydrophobic part of the peptide. These experiments have shown Zn and Fe to be more potent at increasing Aβ aggregation rate and help shed light into understanding amyloid aggregation. Furthermore, the electrochemical technique described here can be applied to study aggregation kinetics of various misfolding proteins.