Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease
Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease
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DOI：
10.1212/wnl.0b013e3181fd613b
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发表时间：
2010-11-16
期刊：
影响因子：
9.9
通讯作者：
El-Agnaf, O. M. A.
中科院分区：
文献类型：
--
作者：
Tokuda, T.;Qureshi, M. M.;El-Agnaf, O. M. A.
背景：迄今为止，还没有公认的基于血液或CSF生化分析的帕金森病（PD）临床诊断试验。在家族性帕金森综合征中编码α-突触核蛋白的SNCA基因突变的发现和α-突触核蛋白在PD脑中的积累表明该蛋白在PD病因学中的关键作用。我们研究了临床诊断为PD、进行性核上性麻痹（PSP）或阿尔茨海默病（AD）的患者和年龄匹配的对照组CSF中的总突触核蛋白和α-突触核蛋白寡聚体水平，结果：与对照组（n = 28）相比，PD组（n = 32; p < 0.0001，Mann-Whitney U检验）中CSF中α-突触核蛋白寡聚体的水平和寡聚体/总α-突触核蛋白的比率更高。受试者工作特征曲线下面积（AUC）显示，临床诊断PD病例中CSF α-突触核蛋白寡聚体增加的灵敏度为75.0%，特异性为87.5%，AUC为0.859。然而，当分析CSF寡聚体/总-α-突触核蛋白比率时，其提供了更高的灵敏度89.3%和特异性90.6%，AUC为0.948。在另一项横断面初步研究中，我们证实PD患者（n = 25）的CSF α-突触核蛋白寡聚体水平高于PSP患者（n = 18; p < 0.05）或AD（n = 35; p < 0.001）或对照受试者（n = 43; p < 0.05）。我们的研究结果表明，CSF中α-突触核蛋白寡聚体的水平和寡聚体/总α-突触核蛋白的水平与CSF中α-突触核蛋白寡聚体的水平有关。突触核蛋白比率可作为诊断和早期检测PD有用的生物标志物。神经病学（R）2010;75：1766-1772
Background: To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding alpha-synuclein in familial parkinsonism and the accumulation of alpha-synuclein in the PD brain suggested a critical role for this protein in PD etiology.Methods: We investigated total and alpha-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory.Results: The levels of alpha-synuclein oligomers and oligomers/total-alpha-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF alpha-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-alpha-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF alpha-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05).Conclusion: Our results demonstrate that levels of alpha-synuclein oligomers in CSF and the oligomers/total-alpha-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD. Neurology (R) 2010;75:1766-1772