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经神经病理学诊断的帕金森病患者的脑脊液生物标志物

Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects.

作者信息

Maarouf Chera L, Beach Thomas G, Adler Charles H, Shill Holly A, Sabbagh Marwan N, Wu Terence, Walker Douglas G, Kokjohn Tyler A, Roher Alex E

机构信息

The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ, USA.

出版信息

Neurol Res. 2012 Sep;34(7):669-76. doi: 10.1179/1743132812Y.0000000063.

Abstract

OBJECTIVES

Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinal fluid (CSF) of neuropathologically confirmed PD cases.

METHODS

We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference gel electrophoresis (2D-DIGE). Spots exhibiting a 1·5-fold or greater difference in volume between PD patients and controls were excised from the two-dimensional gels, subjected to tryptic digestion and identification of peptides assigned using mass spectrometric/data bank correlation methods.

RESULTS

Employing this strategy six molecules: fibrinogen, transthyretin, apolipoprotein E, clusterin, apolipoprotein A-1, and glutathione-S-transferase-Pi, were found to be different between PD and NC populations.

DISCUSSION

These molecules have been implicated in PD pathogenesis. Combining biomarker data from multiple laboratories may create a consensus panel of proteins that may serve as a diagnostic tool for this neurodegenerative disorder.

摘要

目的

帕金森病(PD)影响着约1% - 2%的50岁以上人群。目前尚无治愈方法或有效的病情改善治疗手段,且由于缺乏明确的生物标志物,临床诊断受到困扰。我们试图在神经病理学确诊的PD病例的脑脊液(CSF)中发现潜在的生物标志物。

方法

我们使用二维差异凝胶电泳(2D - DIGE)比较了PD患者和正常对照(NC)受试者的死后脑室脑脊液(V - CSF)。从二维凝胶中切下在PD患者和对照之间体积差异达1.5倍或更大的斑点,进行胰蛋白酶消化,并使用质谱/数据库关联方法鉴定所分配的肽段。

结果

采用该策略发现,纤维蛋白原、转甲状腺素蛋白、载脂蛋白E、簇集蛋白、载脂蛋白A - 1和谷胱甘肽 - S - 转移酶 - Pi这六种分子在PD和NC人群之间存在差异。

讨论

这些分子与PD发病机制有关。整合多个实验室的生物标志物数据可能会形成一个共识性的蛋白质组,可作为这种神经退行性疾病的诊断工具。

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