A protein-based electrochemical biosensor for detection of tau protein, a neurodegenerative disease biomarker.

A protein-based electrochemical biosensor was developed for detection of tau protein aimed towards electrochemically sensing misfolding proteins. The electrochemical assay monitors tau-tau binding and misfolding during the early stage of tau oligomerization. Electrochemical impedance spectroscopy was used to detect the binding event between solution tau protein and immobilized tau protein (tau-Au), acting as a recognition element. The charge transfer resistance (Rct) of tau-Au was 2.9 ± 0.6 kΩ. Subsequent tau binding to tau-Au decreased the Rct to 0.3 ± 0.1 kΩ (90 ± 3% decrease) upon formation of a tau-tau-Au interface. A linear relationship between the Rct and the solution tau concentration was observed from 0.2 to 1.0 μM. The Rct decrease was attributed to an enhanced charge permeability of the tau-tau-Au surface to a redox probe [Fe(CN)6](3-/4-). The electrochemical and surface characterization data suggested conformational and electrostatic changes induced by tau-tau binding. The protein-based electrochemical platform was highly selective for tau protein over bovine serum albumin and allowed for a rapid sample analysis. The protein-based interface was selective for a non-phosphorylated tau441 isoform over the paired-helical filaments of tau, which were composed of phosphorylated and truncated tau isoforms. The electrochemical approach may find application in screening of the early onset of neurodegeneration and aggregation inhibitors.