Neurofilament light: A candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion
Neurofilament light: A candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion
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DOI：
10.1002/ana.25276
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发表时间：
2018-07-01
影响因子：
11.2
通讯作者：
Malaspina, Andrea
中科院分区：
文献类型：
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作者：
Benatar, Michael;Wuu, Joanne;Malaspina, Andrea
目的评估神经丝光（NfL）作为肌萎缩侧索硬化症（ALS）的症状前阶段的生物标志物。方法研究人群包括84个人在发展中国家ALS的风险，34个控制，17个ALS患者，和10个表型转换器（在临床表现的疾病出现之前和之后观察的风险个人）。通过症状前家族性ALS（Pre-fALS）入组高危个体，这是一项纵向自然史和生物标志物研究，研究对象为任何ALS相关基因突变（在SOD 1、C9 orf 72、TARDBP、FUS、VCP等中）的携带者，但在入组时未表现出明显疾病的临床症状或体征（包括肌电图证据）。NfL在血清和脑脊液（CSF）进行定量使用电化学发光immunoassay.ResultsSerum和CSF NfL大幅高于ALS患者相比，对照组和高危人群，并保持相对稳定的时间。然而，在表型转换者中，NfL水平升高（即，高于对照组中观察到的范围），早至出现最早的临床症状或疾病体征之前的大约12个月。InterpretationSerum（和CSF）NfL是症状前ALS的信息性生物标志物，提供了一种新的工具来量化症状前疾病进展并潜在地预测临床表型转换的时间。因此，NfL的定量可以帮助受影响个体的早期治疗干预的设计和实施和/或处于发展ALS的短期风险的个体的疾病预防试验。2018年神经病学年会;83：130-139
ObjectiveTo evaluate neurofilament light (NfL) as a biomarker of the presymptomatic phase of amyotrophic lateral sclerosis (ALS).MethodsThe study population includes 84 individuals at risk for developing ALS, 34 controls, 17 ALS patients, and 10 phenoconverters (at-risk individuals observed both before and after the emergence of clinically manifest disease). At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation (in SOD1, C9orf72, TARDBP, FUS, VCP, etc), but who, at the time of enrollment, demonstrated no clinical symptoms or signs (including electromyographic evidence) of manifest disease. NfL in serum and cerebrospinal fluid (CSF) were quantified using an electrochemiluminescence immunoassay.ResultsSerum and CSF NfL are substantially higher in ALS patients compared to controls and at-risk individuals and remain relatively stable over time. Among phenoconverters, however, NfL levels were elevated (ie, above the range observed in controls) as far back as approximate to 12 months preceding the emergence of the earliest clinical symptoms or signs of disease.InterpretationSerum (and CSF) NfL are informative biomarkers of presymptomatic ALS, providing a new tool to quantify presymptomatic disease progression and to potentially predict the timing of clinical phenoconversion. As such, quantification of NfL may aid the design and implementation of early therapeutic intervention for affected individuals and/or disease prevention trials for individuals at short-term risk of developing ALS. Ann Neurol 2018 Ann Neurol 2018;83:130-139