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

Abstract

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.