Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

神经丝蛋白已被验证为神经轴突损伤的特定体液生物标志物。高灵敏度分析平台的出现能够对血液样本中的神经丝进行可靠的定量并简化纵向随访，为神经丝作为临床实践中的生物标志物的发展铺平了道路。潜在的应用包括评估疾病活动性、监测治疗反应、确定许多急性和慢性神经系统疾病的预后以及将其用作新疗法试验中的结果衡量标准。现在的进展已使神经丝测量进入常规临床实践的门口，以评估个体。在这篇综述中，我们首先概述了有关神经丝结构和功能的当前知识。然后，我们讨论在不同临床背景下确定神经丝水平的分析和统计方法和挑战，并评估神经丝轻链 (NfL) 水平对正常衰老的影响以及解释 NfL 测量值时需要考虑的混杂因素。此外，我们总结了神经丝作为神经轴突损伤生物标志物在一系列神经系统疾病中的当前价值和潜在临床应用，包括多发性硬化症、阿尔茨海默病、额颞叶痴呆、肌萎缩侧索硬化症、中风和脑血管疾病、脑外伤损伤和帕金森病。我们还考虑了完成神经丝从实验室到临床实践中神经系统疾病管理的转化所需的步骤。