Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases
Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases
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DOI：
10.3109/21678421.2014.905606
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发表时间：
2014-09-01
影响因子：
2.8
通讯作者：
Otto, Markus
中科院分区：
文献类型：
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作者：
Feneberg, Emily;Steinacker, Petra;Otto, Markus
TAR DNA 结合蛋白 43 (TDP-43) 是肌萎缩侧索硬化症 (ALS) 和额颞叶变性 (FTLD) 的神经病理学标志之一。它存在于患者的血液和脑脊液（CSF）中；然而，体液中 TDP-43 测量的来源和临床相关性尚不确定。我们通过一维 (1D) 和二维 (2D) 蛋白质免疫印迹 (WB) 和定量质谱 (MRM) 对 ALS、FTLD 和非神经退行性疾病患者的配对 CSF 和血清样本、血液淋巴细胞、脑尿素组分和来自 CSF 的纯化外泌体进行 TDP-43 研究。通过 2D-WB，我们能够证明淋巴细胞、血清和脑脊液中 TDP-43 的同工型模式与具有 TDP-43 病理学的脑尿素组分相比相似。我们发现TDP-43脑脊液与血液的浓度比约为1:200。作为可能的脑特异性部分，我们通过免疫印迹和 MRM 在脑脊液外泌体制剂中发现了 TDP-43。我们得出结论，脑脊液中的TDP-43主要来源于血液。脑脊液和血液中 TDP-43 的测量作为诊断工具并不重要，但对于监测 TDP-43 修饰药物的治疗效果可能很重要。
TAR DNA-binding protein 43 (TDP-43) is one of the neuropathological hallmarks in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). It is present in patients' blood and cerebrospinal fluid (CSF); however, the source and clinical relevance of TDP-43 measurements in body fluids is uncertain. We investigated paired CSF and serum samples, blood lymphocytes, brain urea fractions and purified exosomes from CSF for TDP-43 by one-(1D), and two-dimensional (2D) Western immunoblotting (WB) and quantitative mass spectrometry (MRM) in patients with ALS, FTLD and non-neurodegenerative diseases. By means of 2D-WB we were able to demonstrate a similar isoform pattern of TDP-43 in lymphocytes, serum and CSF in contrast to that of brain urea fractions with TDP-43 pathology. We found that the TDP-43 CSF to blood concentration ratio is about 1:200. As a possible brain specific fraction we found TDP-43 in exosome preparations from CSF by immunoblot and MRM. We conclude that TDP-43 in CSF originates mainly from blood. Measurements of TDP-43 in CSF and blood are of minor importance as a diagnostic tool, but may be important for monitoring therapy effects of TDP-43 modifying drugs.