TY - JOUR
T1 - JNK3 quantification in plasma
T2 - a novel biomarker for neuronal damage in Parkinson's disease
AU - Vacchi, Elena
AU - Giani, Arianna
AU - Perta, Nunzio
AU - Turchetti, Sara
AU - Pasetto, Laura
AU - Bonetto, Valentina
AU - Bacalini, Maria Giulia
AU - Baldelli, Luca
AU - Provini, Federica
AU - Hackethal, Sandra
AU - Riccardi, Silvia
AU - Miano, Silvia
AU - Manconi, Mauro
AU - Kägi, Georg
AU - Bertaina, Ilaria
AU - Bianco, Giovanni
AU - Galati, Salvatore
AU - Kaelin-Lang, Alain
AU - Raimondo, Domenico
AU - Repici, Mariaelena
AU - Tettamanti, Mauro
AU - Melli, Giorgia
AU - Borsello, Tiziana
N1 - This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License,which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
PY - 2025/12/10
Y1 - 2025/12/10
N2 - 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. [Abstract copyright: © 2025. The Author(s).]
AB - 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. [Abstract copyright: © 2025. The Author(s).]
UR - https://www.nature.com/articles/s41531-025-01224-4
U2 - 10.1038/s41531-025-01224-4
DO - 10.1038/s41531-025-01224-4
M3 - Article
C2 - 41372194
SN - 2373-8057
VL - 12
JO - NPJ Parkinson's disease
JF - NPJ Parkinson's disease
IS - 8
ER -