Department of Neurology, Medical University of Graz, Graz, Austria.
Neurochemistry Laboratory Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, Netherlands.
Nat Rev Neurol. 2024 May;20(5):269-287. doi: 10.1038/s41582-024-00955-x. Epub 2024 Apr 12.
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.
神经丝蛋白已被证实为神经轴索损伤的特异性体液生物标志物。高度敏感的分析平台的出现使得能够可靠地定量血液样本中的神经丝，并简化了纵向随访，这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、监测治疗反应以及确定许多急性和慢性神经疾病的预后，以及将其用作新型治疗方法试验的结果测量。目前，神经丝的测量已经发展到可以在常规临床实践中评估个体的阶段。在这篇综述中，我们首先概述了神经丝的结构和功能的现有知识。然后，我们讨论了在不同临床环境下确定神经丝水平的分析和统计方法和挑战，并评估了神经丝轻链（NfL）水平在正常衰老中的意义以及在解释 NfL 测量时需要考虑的混杂因素。此外，我们总结了神经丝作为多种神经疾病（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、创伤性脑损伤和帕金森病）中神经轴索损伤的生物标志物的当前价值和潜在临床应用。我们还考虑了将神经丝从实验室转化为临床实践中神经疾病管理所需的步骤。
