Axonal damage markers in cerebrospinal fluid are increased in ALS

Axonal damage markers in cerebrospinal fluid are increased in ALS
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DOI:
10.1212/01.wnl.0000203120.85850.54
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发表时间:
2006-03-28
期刊:
影响因子:
9.9
通讯作者:
Tumani, H
Tumani, H
中科院分区:
医学1区
文献类型:
--
作者:
Brettschneider, J;Petzold, A;Tumani, H

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目的:检测轴突变性的生物标志物是否与临床亚型相关,并用于预测ALS的进展。研究方法:ALS患者(n = 69),阿尔茨海默病(AD; n = 73)和年龄匹配的对照组(n = 33)被纳入这项前瞻性研究。使用ELISA测量tau蛋白和神经丝(NfH(SMI 35))的CSF水平。在49例ALS患者中,随访数据可用(中位随访时间为7个月)。结果如下:ALS患者CSF中NfHSMI 35水平(1.7 ng/mL)比对照组(0.3 ng/mL,p < 0.001)高5倍,比AD患者(0.14 ng/mL,p < 0.001)高10倍。上运动神经元主导型ALS患者的NfH(SMI 35)值也高于典型ALS(上运动神经元+下运动神经元)患者,p = 0.02。NfH(SMI 35)值在进展更快的ALS中更高。NfH和tau的值与CSF蛋白含量无关。结论:作者提出CSF中的轴突损伤标记物可以区分ALS的亚型,并且它们可以用作治疗试验的标记物。CSF NfH在这些区分中上级tau。
Objective: To test whether biomarkers for axonal degeneration correlated with clinical subtypes and were of use in predicting progression of ALS. Methods: Patients with ALS (n = 69), patients with Alzheimer disease (AD; n = 73), and age-matched controls (n = 33) were included in this prospective study. CSF levels of tau protein and neurofilaments (NfH(SMI35)) were measured using ELISA. In 49 patients with ALS, follow-up data were available (median follow-up 7 months). Results: CSF levels of NfHSMI35 were five times higher in patients with ALS (1.7 ng/mL) than in controls (0.3 ng/mL, p < 0.001) and 10 times higher than in patients with AD (0.14 ng/mL, p < 0.001). NfH(SMI35) values were also higher in patients with upper motor neuron-dominant ALS than in patients with typical ALS (upper motor neuron + lower motor neuron) at p = 0.02. Values of NfH(SMI35) were higher in ALS of more rapid progression. The values of NfH and tau did not correlate with CSF protein content. Conclusions: The authors propose that axonal damage markers in CSF may discriminate between subtypes of ALS and that they could be used as markers for therapeutic trials. CSF NfH was superior to tau in these discriminations.