Rapid Hematological Profiling of the GPNMB/GRN Ratio via Bioelectronic Platform for Early Diagnosis of Parkinson's Disease.

Abstract

Early blood-based diagnosis of Parkinson's disease (PD) remains challenging owing to the lack of reliable composite biomarkers and rapid, sensitive, and cost-effective detection platforms. Here, we report a bioelectronic sensor based on an organic electrochemical transistor (OECT) driven by a laser-induced graphene (LIG) array. By integrating an alternating-current (AC)-mediated LIG rapid incubation system (LRIS), the platform enables multiplexed protein profiling directly from clinical samples within approximately 6 min, with attomolar-level detection limits. We identify the glycoprotein non-metastatic melanoma protein B (GPNMB)/granulin (GRN) ratio as a sensitive composite biomarker of neuroinflammatory dysregulation, showing pronounced alterations at early disease stages and complementing α-synuclein for PD assessment. In PD mouse models spanning mild to severe stages (n = 32), this ratio correlated with disease progression and enabled the detection of mild neuronal loss. Clinical validation in healthy individuals and patients with PD or prodromal PD (n = 54) showed that the GPNMB/GRN ratio distinguished patients with PD from healthy controls with 80% sensitivity, 90% specificity, and 85% accuracy. Incorporating α-synuclein further improved diagnostic accuracy. This biomarker-platform strategy provides a rapid, ultrasensitive, and scalable framework for blood-based PD screening and early risk assessment.