A Rapid Label-Free Electrochemical Detection and Kinetic Study of Alzheimer's Amyloid Beta Aggregation

Abstract

We present the first electrochemical detection, characterization, and kinetic study of the aggregation of Alzheimer's disease (AD) amyloid beta peptides (Abeta-40, Abeta-42) using three different voltammetric techniques at a glassy carbon electrode (GCE). This method is based on detecting changes in the oxidation signal of tyrosine (Tyr) residue. As the peptides aggregate, there are structure conformational changes, which affect the degree of exposure of Tyr to the molecular surface of the peptides. The results show significant differences in the aggregation process between the two peptides, and these correlate highly with established techniques. The method is rapid and label-free, and the principle can be universally applied to other protein aggregation studies related to diseases, such as Huntington's, Parkinson's, and Creutzfeldt Jacob (CJD). This method could also be explored in screening for the effectiveness of AD therapies.

β-Amyloid Biomarker Detection for Alzheimer’s Disease

“…The parameters of the SWV were the following: initial potential 0.4 V, end potential l.0 V, step potential 4 mV, amplitude 25 mV, and frequency 15 Hz. The results showed tyrosine residue's oxidation peak at approximately 0.71 V, which has been reported in other studies [10]. The results also showed that in the presence of metal ions there is a decrease in the intensity of the current, which led them to the conclusion that Zn (II) and Cu (II) affect the morphology of Ab, aggregation kinetics, and have an impact on the oxidation of the tyrosine residue.…”

“…There have been several researches that have used SWV as their main technique of detection, especially in the detection of Ab in the presence of metals [9][10][11]. A study conducted by Hung et al presented the relationship between metal ions like Cu (II), Zn (II) and Fe (II) and the Ab peptide aggregation [9].…”

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

“…In its native form, Ab is unfolded but aggregates into a b-sheet structure of ordered fibrils under various conditions (Stine et al, 2003;Vestergaard et al, 2005). Aggregation is not restricted to pathologically related proteins.…”

Inhibition of Protein Amyloidosis by Glycomaterials

“…On the other hand, electrochemical measurements have broad utility, and are easy to fabricate as simple chip devices. Considering the amino acid sequence, Ab has one tyrosine (Tyr) unit at the 10th residue (24), which has a phenol group on the side chain. The phenol group is subject to oxidation, which was utilized to detect Ab on the substrate (Fig.…”