Recent advances in CSF biomarkers for Parkinson's disease.
Recent advances in CSF biomarkers for Parkinson's disease.
复制标题
帕金森病脑脊液生物标志物的最新进展。
DOI：
10.1016/s1353-8020(11)70017-7
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发表时间：
2012
影响因子：
4.1
通讯作者：
LeWitt,Peter
中科院分区：
文献类型：
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作者：
LeWitt,Peter
虽然帕金森病（PD）的脑脊液（CSF）生物标志物的研究始于40多年前，但最有希望的结果相对较新。在CSF（与脑细胞外液区室相邻）中发现的数百种蛋白质和其他生化物质中，一直在寻找疾病特异性指标。最初，研究集中在PD的选择性神经递质紊乱。虽然多巴胺代谢的研究（如其主要代谢物高香草酸[HVA]所反映的）相对缺乏信息，但我们发现将HVA浓度索引为嘌呤代谢物黄嘌呤的浓度允许区分PD样本与健康对照（p < 0.0016）[Brain Research 2011;1408：88-97]。在另一项最近的生物标志物研究中，我们利用超高效液相色谱法与气相色谱-质谱联用进行代谢组学分析[Movement Disorders 2011;26（Suppl 2）：S193]。使用t检验以p < 0.02区分PD组和对照组，我们发现了未知与神经变性过程相关的化合物的变化（4种CSF浓度增加，8种降低）。最近的其他研究报告了蛋白质和其他生化物质中独特的生物标志物发现。最终目标是在外周生物标本中也发现CSF生物标志物，有助于诊断筛查应用并提供PD病因学的进一步线索。
Though the search for cerebrospinal fluid (CSF) biomarkers of Parkinson's disease (PD) began more than 40 years ago, the most promising results are relatively recent. Disease-specific indicators have been sought among the hundreds of proteins and other biochemicals found in CSF (which is contiguous with the extracellular fluid compartment of the brain). Initially, research focused on the selective neurotransmitter disturbance in PD. While investigations of dopamine metabolism (as reflected by its major metabolite, homovanillic acid [HVA]) have been relatively uninformative, we found that indexing HVA concentration to that of the purine metabolite xanthine permits differentiation of PD specimens from healthy controls (p < 0.0016) [Brain Research 2011;1408:88–97]. In another recent biomarker study, we utilized ultrahigh-performance liquid chromatography linked to gas chromatography-mass spectrometry for metabolomic analysis [Movement Disorders 2011;26(Suppl 2):S193]. Using t-tests to differentiate PD and control groups at p < 0.02, we found changes in compounds not known to be related to the neurodegenerative process (4 increased in CSF concentration and 8 decreased). Other recent investigations have reported distinctive biomarker findings in proteins and other biochemicals. The ultimate goal is for CSF biomarkers also found in peripheral biospecimens, aiding in diagnostic screening applications and providing further clues as to the etiology of PD.