Electrochemical Detection of Amyloid-β Oligomers Based on the Signal Amplification of a Network of Silver Nanoparticles

Amyloid-beta oligomers (A beta Os) are the most important toxic species in the brain of Alzheimer's disease (AD) patient. A beta Os, therefore, are considered reliable molecular biomarkers for the diagnosis of AD. Herein, we reported a simple and sensitive electrochemical method for the selective detection of A beta Os using silver nanoparticles (AgNPs) as the redox reporters and PrP(95-110), an A beta Os-specific binding peptide, as the receptor. Specifically, adamantine (Ad)-labeled PrP(95-110), denoted as Ad-PrP (95-110), induced the aggregation and color change of AgNPs and the follow-up formation of a network of Ad-PrP(95-110)-AgNPs. Then, Ad-PrP(95-110)-AgNPs were anchored onto a beta-cydodextrin (beta-CD) covered electrode surface through the host guest interaction between Ad and beta-CD, thus producing an amplified electrochemical signal through the solid-state Ag/AgCl reaction by the AgNPs. In the presence of A beta Os, Ad-PrP(95-110) interacted specifically with the A beta Os, thus losing the capability to bind AgNPs and to induce the formation of an AgNPs-based network on the electrode surface. Consequently, the electrochemical signal decreased with an increase in the concentration of A beta Os in the range of 20 pM to 100 nM. The biosensor had a detection limit of 8 pM and showed no response to amyloid-beta monomers (A beta Ms) and fibrils (A beta Fs). On the basis of the well-defined and amplified electrochemical signal of the AgNPs-based network architecture, these results should be valuable for the design of novel electrochemical biosensors by marrying specific receptors.