Cerebrospinal fluid (CSF) is a promising clinical sample for identification of novel biomarkers for various neurological disorders. Considering its direct contact with brain tissue, CSF represents a valuable source of brain-related and brain-specific proteins. Multiple sclerosis is an inflammatory, demyelinating neurological disease affecting the central nervous system, and so far there are no diagnostic or prognostic disease specific biomarkers available in the clinic. The primary aim of the present study was to develop a targeted mass spectrometry assay for simultaneous quantification of 30 brain-related proteins in CSF and subsequently to demonstrate assay feasibility in neurological samples derived from multiple sclerosis patients. Our multiplex selected reaction monitoring assay had wide dynamic range (median fold range across peptides = 8.16 × 10³) and high assay reproducibility (median across peptides CV = 4%). Candidate biomarkers were quantified in CSF samples from neurologically healthy individuals (n = 9) and patients diagnosed with clinically isolated syndrome (n = 29) or early multiple sclerosis (n = 15).

中文翻译：

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基于靶向质谱的定量分析30种脑相关蛋白的方法及其临床应用

脑脊液（CSF）是一种有前途的临床样品，可用于鉴定各种神经系统疾病的新型生物标志物。考虑到它与大脑组织的直接接触，CSF代表了大脑相关和大脑特异性蛋白的宝贵来源。多发性硬化症是一种影响中枢神经系统的炎性，脱髓鞘的神经系统疾病，到目前为止，临床上尚无诊断或预后疾病的生物标志物。本研究的主要目的是开发一种靶向质谱分析法，用于同时定量脑脊液中30种与大脑相关的蛋白质，随后证明在多发性硬化症患者的神经系统样本中进行分析的可行性。我们的多重选择反应监测分析具有宽广的动态范围（跨肽段的中位折叠范围= 8）。³）和较高的测定可重复性（跨肽段CV的中位数= 4％）。在神经系统健康个体（n = 9）和诊断为临床孤立综合征（n = 29）或早期多发性硬化症（n = 15）的患者的脑脊液样本中对候选生物标志物进行定量。