Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Neurosci Lett. 2010 Jan 1;468(1):23-7. doi: 10.1016/j.neulet.2009.10.053. Epub 2009 Oct 22.
In amyotrophic lateral sclerosis (ALS) the pathological determinants of disease progression remain poorly understood. We aimed to identify a characteristic CSF protein pattern that could provide new candidate biomarkers of disease progression in ALS.
Using the two-dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with ALS that showed a rapid progression of disease (ALS-rp, n=9) over a follow-up time of 2 years and from patients with ALS that showed a slow progression of disease over follow-up (ALS-sl, n=9) over the same period. Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots ELISA and nephelometry were performed for two candidate proteins on a second cohort of patients (n=40).
We identified 6 different proteins and their isoforms which were all upregulated in ALS-rp as compared to ALS-sl (heat shock protein1, alpha-1 antitrypsin, fetuin-A precursor, transferrin, transthyretin (TTR), nebulin-related anchoring protein). For Fetuin-A and TTR, our findings could be confirmed by quantitative assay.
Fetuin-A and TTR are promising candidate markers for disease progression in ALS that warrant further evaluation on a larger cohort of patients.
在肌萎缩侧索硬化症（ALS）中，疾病进展的病理决定因素仍知之甚少。我们旨在确定一种特征性的 CSF 蛋白图谱，该图谱可能为 ALS 疾病进展提供新的候选生物标志物。
使用二维差异凝胶电泳（2-D-DIGE），我们比较了来自在 2 年内疾病快速进展的 ALS 患者（ALS-rp，n=9）和在同一时期疾病进展缓慢的 ALS 患者（ALS-sl，n=9）的 CSF 样本。选择在患者和对照组之间显示出显著差异的蛋白斑点进行进一步的 MALDI-TOF 质谱分析。为了验证鉴定的斑点，我们在第二个患者队列（n=40）上对两个候选蛋白进行了 ELISA 和散射比浊法检测。
与 ALS-sl 相比，我们在 ALS-rp 中鉴定出 6 种不同的蛋白质及其同工型，均呈上调表达（热休克蛋白 1、α-1 抗胰蛋白酶、胎球蛋白-A 前体、转铁蛋白、转甲状腺素蛋白（TTR）、nebuilin 相关锚定蛋白）。对于胎球蛋白-A 和 TTR，我们的发现可以通过定量测定得到证实。
胎球蛋白-A 和 TTR 是 ALS 疾病进展的有前途的候选标志物，值得在更大的患者队列中进一步评估。
