National Measurement Laboratory, LGC Limited, Teddington TW11 0LY, UK.
Univ. Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, 34295 Montpellier, France.
Int J Mol Sci. 2023 Jul 19;24(14):11624. doi: 10.3390/ijms241411624.
Neurofilament-light chain (Nf-L) is a non-specific early-stage biomarker widely studied in the context of neurodegenerative diseases (NDD) and traumatic brain injuries (TBI), which can be measured in biofluids after axonal damage. Originally measured by enzyme-linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF), Nf-L can now be quantified in blood with the emergence of ultrasensitive assays. However, to ensure successful clinical implementation, reliable clinical thresholds and reference measurement procedures (RMP) should be developed. This includes establishing and distributing certified reference materials (CRM). As a result of the complexity of Nf-L and the number of circulating forms, a clear definition of what is measured when immunoassays are used is also critical to achieving standardization to ensure the long-term success of those assays. The use of powerful tools such as mass spectrometry for developing RMP and defining the measurand is ongoing. Here, we summarize the current methods in use for quantification of Nf-L in biofluid showing potential for clinical implementation. The progress and challenges in developing RMP and defining the measurand for Nf-L standardization of diagnostic tests are addressed. Finally, we discuss the impact of pathophysiological factors on Nf-L levels and the establishment of a clinical cut-off.
神经丝轻链（Nf-L）是一种非特异性的早期生物标志物，在神经退行性疾病（NDD）和创伤性脑损伤（TBI）的研究中得到了广泛研究，可以在轴突损伤后在生物流体中测量。最初通过酶联免疫吸附测定（ELISA）在脑脊液（CSF）中测量，随着超灵敏测定法的出现，现在可以在血液中定量 Nf-L。然而，为了确保成功的临床实施，应开发可靠的临床阈值和参考测量程序（RMP）。这包括建立和分发经过认证的参考物质（CRM）。由于 Nf-L 的复杂性和循环形式的数量，当使用免疫测定法时，明确定义所测量的内容对于实现标准化以确保这些测定法的长期成功也至关重要。正在使用质谱等强大工具来开发 RMP 和定义可测量物。在这里，我们总结了目前用于生物流体中 Nf-L 定量的方法，这些方法显示出了临床应用的潜力。讨论了开发 RMP 和定义诊断测试 Nf-L 标准化的可测量物的进展和挑战。最后，我们讨论了生理病理因素对 Nf-L 水平的影响以及临床截止值的建立。
