Soluble alpha-synuclein (alpha-syn) oligomer is believed to be a reliable molecular biomarker for diagnosis of Parkinson's disease (PD). Thus, it is critical to develop a simple method for the selective detection of alpha-syn oligomer with low cost as well as high sensitivity. In this paper, we reported the label-free detection of alpha-syn oligomer using a DNA aptamer as the bioreceptor with the techniques of gold nanoparticles (AuNPs)-based colorimetric assay, surface plasmon resonance (SPR) and electrochemical impedance spectroscopy (EIS). In the colorimetric assay, the aptamer adsorbed onto the surface of AuNPs to prevent the salt induced aggregation of the nanoparticles. However, the specific binding of alpha-syn oligomer to aptamer prevented the absorption of aptamer onto the surface of AuNPs. As a result, the aggregation of AuNPs was triggered by high concentration of salt with a color change from red to blue. In the SPR- or EIS-based surface analysis, specific binding of alpha-syn oligomer to the aptamer immobilized onto the gold film or electrode surface led to an increase in the SPR dip shift or the electron-transfer resistance. The detection limits of the colorimetry, SPR and EIS were found to be 10 nM, 8 pM and 1 pM, respectively. The amenability of this method to alpha-syn oligomer analysis in a biological matrix was demonstrated by assay of alpha-syn-oligomer in serum. (C) 2017 Elsevier B.V. All rights reserved.