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<p>The prevalence of Parkinson’s disease (PD) is increasing due to the aging population. Early diagnosis and prognosis of PD remain challenging, suggesting that seeking appropriate biomarkers for PD is crucial. Glycoprotein nonmetastatic melanoma protein B (GPNMB) and alpha-synuclein (α-syn) have been reported to contribute to PD pathogenesis and are correlated with PD onset and disease progression. We utilized Mendelian randomization (MR) analysis to elucidate the association of GPNMB and α-syn with PD and its disease progression. Six MR approaches were employed, and inverse variance weighted was chosen as the primary method. MR analysis showed that cerebrospinal fluid (CSF) α-syn correlated with Hoehn and Yahr (H&amp;Y) stage and daytime sleepiness suggestively, indicating that CSF α-syn is a promising biomarker for motor symptoms in PD. Furthermore, reverse MR analysis demonstrated an association between PD and α-syn levels in the parietal lobe cortex. Overall, CSF α-syn is a potential biomarker for predicting PD motor symptoms, which requires further studies to validate. However, no associations between GPNMB and PD risk or disease progression were detected.</p>

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A Mendelian randomization study on association of alpha-synuclein and GPNMB with Parkinson’s disease risk and progression

  • 期刊论文

  • 发表日期：

    2025年4月11日

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  • Lizhi Li,
  • Jiabin Liu,
  • Yige Wang,
  • Zhenhua Liu,
  • Qian Xu,
  • Xinxiang Yan,
  • Beisha Tang,
  • Jifeng Guo

摘要

The prevalence of Parkinson’s disease (PD) is increasing due to the aging population. Early diagnosis and prognosis of PD remain challenging, suggesting that seeking appropriate biomarkers for PD is crucial. Glycoprotein nonmetastatic melanoma protein B (GPNMB) and alpha-synuclein (α-syn) have been reported to contribute to PD pathogenesis and are correlated with PD onset and disease progression. We utilized Mendelian randomization (MR) analysis to elucidate the association of GPNMB and α-syn with PD and its disease progression. Six MR approaches were employed, and inverse variance weighted was chosen as the primary method. MR analysis showed that cerebrospinal fluid (CSF) α-syn correlated with Hoehn and Yahr (H&Y) stage and daytime sleepiness suggestively, indicating that CSF α-syn is a promising biomarker for motor symptoms in PD. Furthermore, reverse MR analysis demonstrated an association between PD and α-syn levels in the parietal lobe cortex. Overall, CSF α-syn is a potential biomarker for predicting PD motor symptoms, which requires further studies to validate. However, no associations between GPNMB and PD risk or disease progression were detected.