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<p>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 (<i>P</i> = 0.048, <i>B</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Elena Vacchi,
  • Arianna Giani,
  • Nunzio Perta,
  • Sara Turchetti,
  • Laura Pasetto,
  • Valentina Bonetto,
  • Maria Giulia Bacalini,
  • Luca Baldelli,
  • Federica Provini,
  • Sandra Hackethal,
  • Silvia Riccardi,
  • Silvia Miano,
  • Mauro Manconi,
  • Georg Kägi,
  • Ilaria Bertaina,
  • Giovanni Bianco,
  • Salvatore Galati,
  • Alain Kaelin-Lang,
  • Domenico Raimondo,
  • Mariaelena Repici,
  • Mauro Tettamanti,
  • Giorgia Melli,
  • Tiziana Borsello

摘要

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.