Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS
Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS
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DOI：
10.1002/acn3.50943
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发表时间：
2019-11-19
影响因子：
5.3
通讯作者：
Tokuda, Takahiko
中科院分区：
文献类型：
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作者：
Kasai, Takashi;Kojima, Yuta;Tokuda, Takahiko
目的：探讨肌萎缩侧索硬化症(ALS)患者脑脊液(CSF)和血浆中神经丝轻链(NIL)、TAR DNA结合蛋白43(TDP-43)和总tau(t-tau)的检测对ALS的诊断和预后判断的意义，并探讨其联合应用能否提高ALS的诊断水平。方法：这是一项单中心、前瞻性、纵向研究。脑脊液和血浆样本是在登记时从29名ALS患者和29名年龄匹配的未患神经退行性疾病的对照组中收集的。在验证队列中，有46名ALS患者和46名对照组(未配对)因神经肌肉疾病导致的运动无力。采用超灵敏单分子分析(SIMOA)技术检测脑脊液和血浆中NIL、TDP-43和t-tau水平。结果：在发现和验证队列中可重复地观察到以下发现：与对照组相比，ALS患者的脑脊液NFL、血浆NFL和脑脊液TDP-43水平升高；与脑脊液和血浆NIL水平升高相关的生存期缩短。当脑脊液NFL和脑脊液TDP-43水平联合检测时，仅就每个生物标志物而言，ROC曲线下面积(AUC)相对于AUC略有改善。解释：脑脊液和血浆神经营养因子不仅可以作为诊断生物标记物，还可以作为疾病进展的指标。脑脊液TDP-43也可作为ALS的诊断生物标志物，但没有预后价值。联合检测脑脊液NFL和脑脊液TDP-43可能是诊断ALS的有用生物标志物。
Objective: To determine the diagnostic and prognostic significance of neurofilament light chain (NIL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods: This was a single-center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age-matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not agematched) patients with motor weakness resulting from neuromuscular diseases. NIL, TDP-43, and t-tau levels in CSF and plasma were measured using ultra-sensitive single molecule assay (Simoa) technology. Results: The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP-43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NIL. When the CSF Nfl, and CSF TDP-43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation: CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP-43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP-43 may be a useful biomarker for the diagnosis of ALS.