Szejko Natalia, Picón Carmen, García-Caldentey Juan, de Yebenes Justo Garcia, Alvarez-Cermeño Jose Carlos, Villar Luisa Maria, López-Sendón Moreno José Luis
Department of Neurology, Medical University of Warsaw, Poland; Department of Bioethics, Medical University of Warsaw, Poland.
Servicio de Inmunología. Hospital Ramón y Cajal. Madrid. Spain.
PLoS Curr. 2018 Aug 31;10:ecurrents.hd.280c8f9f7d9fa4f7f0c883d9f8e807da. doi: 10.1371/currents.hd.280c8f9f7d9fa4f7f0c883d9f8e807da.
Neurofilament light proteins (NFL) are a structural element of the neuronal cytoskeleton and are released with neuronal damage. Its levels are increased in cerebrospinal fluid (CSF) in the setting of neurodegenerative diseases. We investigated the CSF-NFL levels of Huntington´s disease (HD) patients (participating in a clinical trial SAT-HD) as well as of premanifest carriers and compared their results with a sample of healthy controls and correlated CSF-NFL levels with demographic and clinical variables (baseline demographic characteristics and HD measures of disease severity). CSF levels were significantly higher in all HD subjects [5014.4 (1557.3) ng/l] and pre-manifest carriers [1050 (212.13) ng/l as compared to controls [331.4 (200.2) ng/l] (p<0.00) and were correlated with age (correlation coefficient -0.37, p<0.01) and CAG triplet number (0,51, p<0.05) in the subset of HD patients. NFL levels were not correlated with age in the control group. We did not find any correlation with the remaining variables. These results indicate, as in previous studies, that CSF-NFL levels are a marker of neuronal damage in HD. It seems to be a highly sensitive, but non-specific marker of axonal damage. One of the limitations of our study is a very small number of patients in pre-symptomatic group and lack of individuals with very advanced HD. Further investigations should focus on study of CSF-NFL levels in advanced patients, tracking prospectively CSF-NFL levels and analysing its correlation with the clinical course and usefulness to monitor disease progression, validation and quantification of NFL levels in more accessible biofluids.
神经丝轻链蛋白（NFL）是神经元细胞骨架的一种结构成分，在神经元受损时会被释放出来。在神经退行性疾病的情况下，其在脑脊液（CSF）中的水平会升高。我们研究了亨廷顿舞蹈病（HD）患者（参与临床试验SAT - HD）以及症状前携带者的脑脊液NFL水平，并将他们的结果与健康对照组样本进行比较，还将脑脊液NFL水平与人口统计学和临床变量（基线人口统计学特征以及HD疾病严重程度指标）进行关联分析。所有HD受试者的脑脊液水平[5014.4（1557.3）ng/l]和症状前携带者的脑脊液水平[1050（212.13）ng/l]均显著高于对照组[331.4（200.2）ng/l]（p<0.00），并且在HD患者亚组中与年龄（相关系数 -0.37，p<0.01）和CAG三联体数目（0.51，p<0.05）相关。在对照组中，NFL水平与年龄无关。我们未发现其与其余变量存在任何关联。这些结果表明，与先前的研究一样，脑脊液NFL水平是HD中神经元损伤的一个标志物。它似乎是轴突损伤的一个高度敏感但非特异性的标志物。我们研究的局限性之一是症状前组患者数量非常少，并且缺乏HD晚期患者。进一步的研究应聚焦于晚期患者脑脊液NFL水平的研究，前瞻性地跟踪脑脊液NFL水平，并分析其与临床病程的相关性以及监测疾病进展、验证和量化更易获取生物流体中NFL水平的效用。
