Neuronal Tau Protein Self-Assembly on Gold Surface: Electrochemical Impedance Spectroscopy and Cyclic Voltammetry Studies

Abstract

Tau is a neuronal protein responsible for microtubule formation [1]. It is also the pathological protein active in the Alzheimer’s Disease (AD) pathway. When Tau begins to aggregate as a result of misfolding, the neuronal cells die due to the lack of microtubule formation and can take on prion-like properties [2]. Therefore, detection of aggregated Tau can serve as a powerful tool in the early diagnosis of AD and dementia related diseases. As has been previously demonstrated, Tau 441 can be detected with an electrochemical immunoassay based on the electrochemical impedance spectroscopy (EIS) by using gold electrode [3]. The EIS was also used to monitor interactions between Tau protein and Heparin [4]. Herein, we describe use of EIS and cyclic voltammetry (CV) to monitor and detect self-assembly of Tau protein on gold electrode. After modifying the surface of the electrode with Tau, the aggregation of Tau was performed using Heparin, as an aggregation inducer. The EIS and CV were measured as a function of Tau or Heparin concentrations, and incubation time and temperature. The control experiments included, Tau-free surface, Heparin-free solution, buffer solution in order to minimize aggregation. The charge transfer resistance, Rct, was determined by fitting the experimental data to the equivalent circuit. The Rct values for Tau-films on gold surface were compared prior and post aggregation. The Rct values were highly dependent on the experimental conditions used and that the electrochemical methods are promising sensing platforms for detection of neurodegenerative biomarkers which undergo self-assembly and aggregation.