Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease.
Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease.
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DOI：
10.1186/s13024-016-0072-9
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发表时间：
2016-01-19
影响因子：
15.1
通讯作者：
El-Agnaf OM
中科院分区：
文献类型：
--
作者：
Majbour NK;Vaikath NN;van Dijk KD;Ardah MT;Varghese S;Vesterager LB;Montezinho LP;Poole S;Safieh-Garabedian B;Tokuda T;Teunissen CE;Berendse HW;van de Berg WD;El-Agnaf OM
尽管经过了数十年的深入研究，迄今为止，还没有基于血液或CSF的生化分析的帕金森病（PD）的公认诊断。然而，PD患者大脑中的神经变性在临床症状出现之前几年就开始了，这表明这种方法存在严重的缺陷/局限性。为了探索α-突触核蛋白（α-syn）种类作为PD候选生物标志物的潜在用途，我们制备了针对各种α-syn种类的特异性抗体，即总-、寡聚-和磷酸化-Ser 129-α-syn（t-、o-和p-S129-α-syn）。接下来，我们试图利用我们的抗体开发高度特异性的ELISA测定，以定量生物样品中的α-syn种类。最后，我们验证了我们的检测方法在46例PD患者和48例年龄匹配的健康对照的CSF样本中的有用性。我们还评估了将多种CSF α-syn种类与经典阿尔茨海默病生物标志物相结合的区分能力。CSF o-/t-α-syn、p-S129-α-syn和p-tau的组合提供了区分PD患者与对照的最佳拟合预测模型。此外，CSF o-α-syn水平与PD运动症状的严重程度显著相关（r = -0.37）。我们的新ELISA检测可作为研究工具，以解决PD和相关疾病对可靠CSF生物标志物的未满足需求。本文的在线版本（doi：10.1186/s13024-016-0072-9）包含补充材料，可供授权用户使用。
Despite decades of intensive research, to date, there is no accepted diagnosis for Parkinson’s disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before the manifestation of the clinical symptoms, pointing to serious flaw/limitations in this approach. To explore the potential use of alpha-synuclein (α-syn) species as candidate biomarkers for PD, we generated specific antibodies directed against wide array of α-syn species, namely total-, oligomeric- and phosphorylated-Ser129-α-syn (t-, o- and p-S129-α-syn). Next we sought to employ our antibodies to develop highly specific ELISA assays to quantify α-syn species in biological samples. Finally we verified the usefulness of our assays in CSF samples from 46 PD patients and 48 age-matched healthy controls. We also assessed the discriminating power of combining multiple CSF α-syn species with classical Alzheimer’s disease biomarkers. The combination of CSF o-/t-α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients from controls. Moreover, CSF o-α-syn levels correlated significantly with the severity of PD motor symptoms (r = -0.37). Our new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders. The online version of this article (doi:10.1186/s13024-016-0072-9) contains supplementary material, which is available to authorized users.