Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: Specificity, sensitivity, and a possible prognostic value
Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: Specificity, sensitivity, and a possible prognostic value
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DOI：
10.3109/17482968.2010.541263
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发表时间：
2011-03-01
影响因子：
--
通讯作者：
Kuwabara, Satoshi
中科院分区：
文献类型：
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作者：
Noto, Yu-Ichi;Shibuya, Kazumoto;Kuwabara, Satoshi
TAR DNA结合蛋白（TDP-43）可能是肌萎缩侧索硬化（ALS）的主要致病蛋白。先前的研究表明，ALS患者通过ELISA测量的CSF中TDP-43的水平显著高于对照组。本研究的目的是调查CSF TDP-43水平升高是否是ALS特有的，并且与ALS患者的临床特征相关。我们用同样的ELISA法检测了27例ALS患者和50例神经退行性或炎症性疾病对照（如帕金森病、多发性硬化症和格林-巴利综合征）的CSF TDP-43水平，结果显示仅ALS患者CSF TDP-43水平升高。受试者工作特征（ROC）分析显示敏感性为59.3%，特异性为96.0%。我们还发现较低的CSF TDP-43水平可能与较短的生存时间相关。总之，CSF TDP-43是支持ALS诊断的潜在生物标志物。此外，在ALS患者中，CSF TDP-43水平较低可能反映了TDP-43在皮质和脊髓运动神经元中的积累，从而缩短了生存时间，尽管这应该在更大的前瞻性研究中得到证实。
TAR DNA binding protein of 43 kDa (TDP-43) is likely to be the major pathogenetic protein in amyotrophic lateral sclerosis (ALS). A previous study has shown that levels of TDP-43 in CSF measured by an ELISA are significantly higher for ALS patients than for controls. The aim of this study was to investigate whether elevated CSF TDP-43 levels are specific to ALS, and are associated with clinical profiles in ALS patients. We measured CSF TDP-43 levels by the same ELISA in 27 ALS patients and 50 neurodegenerative or inflammatory disease controls such as Parkinson's disease, multiple sclerosis, and Guillain-Barre, syndrome.Results showed that the CSF TDP-43 levels were increased only in ALS patients. Receiver operating characteristic (ROC) analyses showed a sensitivity of 59.3% and a specificity of 96.0%. We also found that lower CSF TDP-43 levels may be associated with shorter survival time. In conclusion, the CSF TDP-43 is a potential biomarker that supports a diagnosis of ALS. Moreover, among ALS patients, lower levels of CSF TDP-43 may reflect the accumulation of TDP-43 in the cortical and spinal motor neurons and thereby shorter survival time, although this should be confirmed in larger prospective studies.