Protein aggregation of alpha-synuclein (α-Syn) is implicated in Parkinson’s disease (PD), and, thus, α-Syn aggregates are a potentially promising candidate biomarker for PD diagnosis. Here, we describe a simple and sensitive electrochemical sensor to monitor the aggregation of α-Syn for early PD diagnosis. The sensor utilizes methylene blue (MB)-tagged aptamer (Apt) adsorbed on electrochemically reduced graphene oxide (ERGO) by π–π stacking. The binding of α-Syn oligomer to the Apt induces desorption of the Apt from the ERGO surface, which leads to the electrochemical signal change. The resulting sensor allowed the highly sensitive and selective detection of α-Syn oligomer according to the voltammetric change. Under optimized conditions, the linear range of detection was observed to be from 1 fM to 1 nM of the α-Syn oligomer and the limit of detection (LOD) was estimated to be 0.64 fM based on S/N = 3. The sensor also showed good reproducibility and stability, enabling real sample analysis of the α-Syn oligomer in human blood serum. With its ultrasensitivity and good performance for α-Syn oligomer detection, the sensor provides one promising tool for the early diagnosis of PD.

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