Differential diagnosis of amyotrophic lateral sclerosis from Guillain-Barre syndrome by quantitative determination of TDP-43 in cerebrospinal fluid
Differential diagnosis of amyotrophic lateral sclerosis from Guillain-Barre syndrome by quantitative determination of TDP-43 in cerebrospinal fluid
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DOI：
10.3109/00207454.2013.848440
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发表时间：
2014-05-01
影响因子：
2.2
通讯作者：
Akiyama, Haruhiko
中科院分区：
文献类型：
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作者：
Hosokawa, Masato;Arai, Tetsuaki;Akiyama, Haruhiko
本研究的目的是探讨脑脊液（CSF）中TAR DNA结合蛋白43（TDP-43）水平的升高是否可以作为肌萎缩侧索硬化（ALS）的生物标志物，并有助于ALS与周围运动神经病的鉴别诊断。TDP-43是神经元和神经胶质内含物的主要成分，其在神经病理学上表征ALS和tau阴性额颞叶变性。最近在家族性ALS中TDP-43基因中发现的各种错义突变表明TDP-43的异常积累在神经变性中起关键作用。CSF中TDP-43的增加可能是ALS和其他TDP-43蛋白病的标志。建立了测定生物体液中TDP-43浓度的双抗体夹心酶联免疫吸附法（ELISA）。用各种TDP-43构建体转染的细胞的培养上清液用于确认ELISA检测到TDP-43。通过免疫沉淀和随后的免疫印迹检测TDP-43转染细胞的培养上清液中的TDP-43，并通过夹心ELISA成功地测量浓度。然后，我们测量了ALS和格林-巴利综合征（GBS）患者CSF中TDP-43的浓度。ALS患者CSF中TDP-43浓度显著高于GBS患者（p = 0.016）。诊断试验的敏感性为71.4%，特异性为84.6%。通过夹心ELISA定量测定CSF中的TDP-43浓度是区分ALS与周围运动神经病如GBS的潜在实验室测试。
The aim of this study was to investigate whether an increased level of TAR DNA-binding protein 43 (TDP-43) in the cerebrospinal fluid (CSF) could be a biomarker for amyotrophic lateral sclerosis (ALS) and facilitate differential diagnosis of ALS from peripheral motor neuropathy. TDP-43 is the major constituent of neuronal and glial inclusions that neuropathologically characterize both ALS and tau-negative frontotemporal lobar degeneration. Recent discoveries of various missense mutations in the TDP-43 gene in familial ALS indicate a pivotal role of the aberrant accumulation of TDP-43 in neurodegeneration. Increased TDP-43 in the CSF could be a hallmark of ALS and other TDP-43 proteinopathy. Sandwich enzyme-linked immunosorbent assay (ELISA) was established to measure the concentration of TDP-43 in biological fluids. Culture supernatants of cells transfected with various TDP-43 constructs were used to confirm that the ELISA detected TDP-43. TDP-43 in the culture supernatant of TDP-43 transfected cells was detected by immunoprecipitation with subsequent immunoblotting and concentrations were successfully measured by sandwich ELISA. We then measured TDP-43 concentrations in the CSF of patients with ALS and Guillain-Barre syndrome (GBS). TDP-43 concentrations in CSF were significantly higher in ALS than in GBS (p = 0.016). The sensitivity of the diagnostic test was 71.4% and the specificity was 84.6%. Quantitative determination of TDP-43 concentrations in the CSF by sandwich ELISA is a potential laboratory test for differentiating ALS from peripheral motor neuropathies such as GBS.