Table_1_Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value.XLSX

Neurofilament-light chain (NF-L) is a well-known clinical biomarker of many neurodegenerative diseases. By analyzing amyotrophic lateral sclerosis (ALS) patients cerebrospinal fluid (CSF) or plasma, progression of NF-L levels can forecast conversion from the presymptomatic to symptomatic stage and time of survival. The use of plasma for NF-L measurement makes this biomarker exceptionally valuable for clinical studies since sample collection can be performed repeatedly without causing much harm. Detailed analyses of NF-L expression in neurodegenerative disease patient’s samples were already performed, while NF-L levels of preclinical models of ALS, Alzheimer’s and Parkinson’s disease as well as lysosomal storage diseases are still widely unknown. We therefore evaluated NF-L levels in the plasma of the ALS models SOD1-G93A low expressor and TAR6/6 mice, the Alzheimer’s disease (AD) model 5xFAD, the Parkinson’s disease model Line 61 and the Gaucher disease (GD) model 4L/PS-NA and the CSF of selected models. Our results show that NF-L levels are highly increased in the plasma of ALS, Alzheimer’s and GD models, while in the analyzed Parkinson’s disease model NF-L plasma levels barely changed. Most analyzed models show a progressive increase of NF-L levels. NF-L measurements in the plasma of the neurodegenerative disease mouse models of ALS and AD are thus a good tool to evaluate disease progression. Compared to analyses in human tissues, our results suggest a high translation value of murine NF-L levels and their progression. Furthermore, our data indicate that NF-L might also be a good biomarker for disorders with a neuronal component like some lysosomal storage diseases.

神经纤维蛋白轻链（NF-L）是众多神经退行性疾病公认的临床生物标志物。通过对肌萎缩侧索硬化症（ALS）患者脑脊液（CSF）或血浆的分析，NF-L水平的升高可预测从无症状期向症状期的转变以及生存时间的长短。由于血浆样本的采集可反复进行而不会造成严重伤害，因此，利用血浆进行NF-L测量使得这一生物标志物在临床研究中显得尤为珍贵。对于神经退行性疾病患者样本中NF-L表达的详细分析业已进行，然而，包括ALS、阿尔茨海默病和帕金森病以及溶酶体储存病在内的临床前模型中NF-L水平的研究尚处于未知状态。因此，本研究评估了ALS模型SOD1-G93A低表达者、TAR6/6小鼠、阿尔茨海默病模型5xFAD、帕金森病模型Line 61以及戈谢病（GD）模型4L/PS-NA的血浆中NF-L水平以及选定模型的CSF。我们的结果显示，ALS、阿尔茨海默病和GD模型的血浆中NF-L水平显著升高，而在所分析的帕金森病模型中，NF-L血浆水平几乎无变化。大多数分析模型显示NF-L水平呈逐渐上升趋势。因此，ALS和AD神经退行性疾病小鼠模型血浆中的NF-L测量是评估疾病进展的良好工具。与人类组织中的分析相比，我们的结果表明，小鼠NF-L水平及其进展具有较高的转化价值。此外，我们的数据还表明，NF-L可能也是某些具有神经元成分的疾病（如某些溶酶体储存病）的良好生物标志物。