Peptide-based electrochemical sensor for sensitive detection of amyloid-β oligomer with laccase-mimicking nanozyme assemblies as a signal amplifier

Amyloid-β (Aβ) protein is a notable blood biomarker of Alzheimer's disease, and achieving its sensitive detection is a current research hotspot in medicine. Herein, a sandwich-type electrochemical sensor is developed to detect Aβ oligomer 42 (AβO-42, abbreviated as AβO) sensitively. It uses peptide and aptamer as the recognition element, and the laccase-mimicking nanozyme assemblies (denoted as CH-Cu-NAs) as the signal amplifier. AβO is captured by specific peptide pre-modified using gold nanoparticles. Next, the CH-Cu-NAs are modified using an aptamer that binds to targets, resulting in a peptide/target/aptamer sandwich-type sensor. The CH-Cu-NAs are used as an amplification unit, which can oxidize hydroquinone into benzoquinone, and stripping peak currents of the oxidation reaction are used to monitor the AβO level. The proposed method achieves a detection range of 0.05–5 nM with a limit of detection at 0.0192 nM, representing over a 10-fold enhancement in sensitivity relative to conventional peptide-based electrochemical biosensors for AβO. This good sensitivity is attributed to the three-dimensional arrangement of the CH-Cu-NAs enhances the capture efficiency. The sensor also achieves satisfactory results in actual serum samples. The orderly binding of nanozyme monomers and their application as signal amplifiers can offer novel strategies for electrochemically sensitive detection of biomarkers.