JNK3 quantification in plasma: a novel biomarker for neuronal damage in Parkinson’s disease

Diagnosis of Parkinson’s disease (PD) remains challenging due to the lack of reliable biomarkers. To address this need, we quantified plasma levels of brain-specific c-Jun N-terminal kinase 3 (JNK3), a protein involved in neurodegeneration. A total of 108 participants were enrolled, including 25 individuals with isolated REM sleep behavior disorder (iRBD), 26 patients with De Novo PD, 29 with Late PD, and 28 age-matched healthy controls (HC). All subjects underwent clinical assessment, blood sampling, and skin biopsy. Plasma JNK3 levels were significantly elevated in PD and iRBD compared to HC, a finding that remained robust after adjustment for age and sex in multivariate logistic regression. ROC analysis demonstrated that JNK3 levels distinguished PD from HC with 100% specificity and 65% sensitivity in Late PD. In contrast, Neurofilament Light Chain showed non-significant group differences and weak discriminative performance. Notably, while JNK3 declined with age in HC, it increased with age in Late PD (P = 0.048, B = 0.105) and negatively correlated with motor impairment. Elevated JNK3 was also associated with pathological α-Synuclein in skin biopsy. These findings highlight JNK3 as a promising blood biomarker for PD, with meaningful diagnostic and prognostic value, suggesting that its implementation could refine patient stratification and improve clinical trial efficiency.