A MicroRNA (miR) based electrochemical method for quantification of miR-146a, a known biomarker for neurodegenerative disease, was developed. In this bioassay, the capture microRNA (C-miR) was self-assembled on the gold surface and used for quantification of target microRNA (T-miR) of miR-146a. For this purpose, an optimized concentration of C-miR was immobilized on the surface of gold electrode and used for capture of target analyte (T-miR). All of preparation steps were characterized by electrochemical techniques (cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS)) and atomic force microscopy (AFM). At the optimized conditions, the linear dynamic range, limit of quantification and relative standard deviation of the proposed bioassay were obtained as 10 pM to 1 mu M, 10 pM and 1.59%, respectively. The unprocessed human serum sample was used as a real sample and the results fully confirm that the designed microRNA based biosensor is capable for detection of miR-146a as neurodegenerative disease biomarker. The developed method offers a more precise and high sensitive tool to be used in clinical applications for early detection of neurodegenerative disease like Alzheimer's and Parkinson. (C) 2019 Elsevier B.V. All rights reserved.