Mendelian Randomization Analysis Reveals No Causal Relationship Between Plasma α-Synuclein and Parkinson’s Disease

Zhang, Qi; Lin, Zenan; He, Yan; Jiang, Jingzhi; Hu, Di

doi:10.1007/s12035-023-03206-0

Cited by 1 publication

(1 citation statement)

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“…Zubelzu et al conducted a meta-analysis on plasma α-syn levels in individuals with PD, supporting the idea that plasma α-syn levels increase in the early stages of PD [39]. Conversely, a Mendelian Randomization analysis exploring the relationship between plasma α-syn and PD revealed no causative relationship, coinciding with our results [40]. Additionally, the levels of plasma α-syn are also signi cantly related to clinical features of PD, including lower age, shorter disease duration and milder motor impairment [39], and the results of the study also showed that higher levels of plasma α-syn were associated with a lower H&Y stage.…”

Section: Discussionsupporting

confidence: 90%

A Mendelian Randomization Study on Association of Alpha-synuclein and GPNMB with Parkinson’s Disease Risk and Progression

Guo,

Li,

Liu

et al. 2024

Preprint

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The prevalence of Parkinson’s disease (PD) is increasing because of the aging population. Early diagnosis and prognosis of PD remain challenging, suggesting that seeking appropriate biomarkers for PD is crucial. 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. Five MR methods were employed, and inverse variance weighted was chosen as the primary method. The results of MR analysis showed that cerebrospinal fluid (CSF) α-syn correlated with the Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ) and Hoehn and Yahr (H&Y) stage, and plasma α-syn was associated with H&Y stage at baseline suggestively, indicating that α-syn is a promising biomarker for motor symptoms of PD. Overall, CSF and plasma α-syn are potential biomarkers for predicting PD motor symptoms, which warrant further studies. However, no association was detected between GPNMB and PD risk or disease progression.

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Section: Discussionsupporting

confidence: 90%