Pedersen Camilla Christina, Alves Guido, Tysnes Ole-Bjørn, Maple-Grødem Jodi, Lange Johannes
Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
Eur J Neurol. 2025 Jun;32(6):e70167. doi: 10.1111/ene.70167.
Alpha-synuclein (α-syn), phosphorylated at serine 129 (pS129-α-syn), is a potential biomarker for Parkinson's disease (PD) because it is the predominant α-syn species found in Lewy bodies.
We developed an in-house SIMOA assay, using commercially available components, to quantify pS129-α-syn in CSF. The clinical utility of the assay was tested in CSF from 120 patients with PD from the Norwegian ParkWest longitudinal study and 29 normal controls. Prior measurements of CSF total (t)-α-syn and the pS129-α-syn/t-α-syn ratio were included for comparison.
The lower limit of quantification of the in-house assay used to analyze CSF samples from participants was 0.57 pg/mL, which was well below the observed concentrations of endogenous pS129-α-syn in CSF. Median CSF pS129-α-syn levels were slightly lower in PD patients compared to controls (5.7 pg/mL vs. 6.5 pg/mL), but the difference was not significant in the unadjusted (p = 0.404) or adjusted analyses (p = 0.270). There was no difference in the pS129-α-syn/t-α-syn ratio between patients and controls. Using linear mixed-effects models, we found no association between baseline pS129-α-syn or the pS129-α-syn/t-α-syn ratio and motor or cognitive decline over a 10-year period.
We developed and applied an in-house SIMOA that reliably quantifies pS129-α-syn in CSF samples. This study does not indicate a role for CSF pS129-α-syn or the pS129-α-syn/t-α-syn ratio as clinically useful diagnostic or prognostic biomarkers in PD.
丝氨酸129位点磷酸化的α-突触核蛋白（pS129-α-syn）是帕金森病（PD）的潜在生物标志物，因为它是路易小体中主要的α-突触核蛋白种类。
我们使用市售组件开发了一种内部单分子阵列免疫检测法（SIMOA），用于定量脑脊液中的pS129-α-syn。该检测法的临床实用性在挪威ParkWest纵向研究的120例PD患者和29例正常对照的脑脊液中进行了测试。还纳入了先前对脑脊液总（t）-α-突触核蛋白和pS129-α-syn/t-α-突触核蛋白比值的测量结果进行比较。
用于分析参与者脑脊液样本的内部检测法的定量下限为0.57 pg/mL，远低于脑脊液中内源性pS129-α-syn的观察浓度。与对照组相比，PD患者脑脊液中pS129-α-syn的中位数水平略低（5.7 pg/mL对6.5 pg/mL），但在未调整分析（p = 0.404）或调整分析（p = 0.270）中差异均不显著。患者与对照组之间的pS129-α-syn/t-α-突触核蛋白比值没有差异。使用线性混合效应模型，我们发现基线pS129-α-syn或pS129-α-syn/t-α-突触核蛋白比值与10年内的运动或认知衰退之间没有关联。
我们开发并应用了一种内部SIMOA，可可靠地定量脑脊液样本中的pS129-α-syn。本研究未表明脑脊液pS129-α-syn或pS129-α-syn/t-α-突触核蛋白比值在PD中作为临床有用的诊断或预后生物标志物的作用。
