Alpha-synuclein (α-synuclein) is a key biomarker for neurodegenerative diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Its early and accurate detection in biological samples is crucial for timely diagnosis and disease management. This study presents a dual-platform biosensor that integrates electrochemical impedance spectroscopy (EIS) and surface plasmon resonance (SPR) for highly sensitive and specific α-synuclein quantification.

The electrochemical biosensor is based on nanostructured gold electrodes functionalized with monoclonal antibodies that selectively capture α-synuclein, inducing measurable impedance changes upon binding. SPR-based optical detection provides a label-free, real-time analysis of the same interaction, allowing for the cross-validation of results. The sensor was tested using spiked and clinical samples, demonstrating a detection limit of 12.5 pM (EIS) and 8.3 pM (SPR), with a linear range of 10 pM–100 nM. Both techniques exhibited high specificity, effectively distinguishing α-synuclein from common biofluid interferents.

This dual-detection strategy enhances the reliability, reproducibility, and accuracy of α-synuclein quantification, providing complementary insights into biomarker interactions. Furthermore, the biosensor's design enables potential miniaturization for portable point-of-care (POC) diagnostics, facilitating early intervention and improved disease monitoring. By integrating advanced biosensing technologies, this study addresses key challenges in biomarker detection, paving the way for more accessible and effective clinical diagnostics for neurodegenerative diseases.