Electrochemical biosensors have been used to detect biomarkers sensitively at low limits of detection. The organic electrochemical transistor (OECT) is a special class of electrochemical biosensors characteristically known for its intrinsic amplification abilities. Nevertheless, if the biosensor is to be used with real clinical samples a strategy aiming to increase the specificity of the device other than the dependance on the respective biorecognition unit is necessary to minimize, if not eliminate, interference from foulants in complex biological media. In this work we test the antifouling performance of several Poly(ethylene glycol) based SAMs using Electrochemical impedance spectroscopy (EIS). We also evaluate the overall performance of the device and its ability to detect total α-synuclein, its aggregate and phosphorylated forms spiked in heat-inactivated human serum. Limits of detection in the fM and aM ranges were achieved.