Advances and challenges in electrochemical detection of α-synuclein: Toward precision diagnosis of Parkinson's disease.

Abstract

α-Synuclein (α-Syn) is a pivotal biomarker for Parkinson's disease (PD) and related synucleinopathies. However, the sensitive and selective detection of pathological α-Syn remains highly challenging because of its low abundance, structural heterogeneity, and diverse aggregation states. No single analytical platform currently meets all requirements for routine clinical screening. Electrochemical biosensors have emerged as a powerful tool to address these bottlenecks, offering high sensitivity, rapid response, low cost, and great potential for point-of-care testing (POCT). This review systematically summarizes the role of α-Syn in PD pathogenesis and highlights recent advances in electrochemical detection strategies, including immunosensors, aptasensors, molecularly imprinted polymers (MIPs), electrochemiluminescence (ECL), photoelectrochemical (PEC) systems, and integrated portable devices. Furthermore, current challenges are emphasized, particularly in low-abundance detection, matrix interference, conformational discrimination, and clinical standardization. Finally, future perspectives in this field are outlined, focusing on multiplex biomarker platforms and artificial intelligence (AI)-assisted analytical strategies for the early diagnosis and management of neurodegenerative diseases.