Section of Neurology, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Alzheimers Res Ther. 2018 Jan 23;10(1):8. doi: 10.1186/s13195-018-0339-1.
Cerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable marker of neuro-axonal damage in different neurological disorders that is related to disease severity. To date, all recent studies performed in human CSF have used the same enzyme-linked immunosorbent assay (ELISA). To confirm the large body of evidence for NfL, we developed a new ELISA method and here we present the performance characteristics of this new ELISA for CSF NfL in different neurological disorders.
We produced two monoclonal antibodies (NfL21 and NfL23) directed against the NfL core domain, and developed a novel sandwich ELISA method that we evaluated in patients with: 1) inflammatory demyelinating diseases (IDD; n = 97), including multiple sclerosis (MS; n = 59), clinically isolated syndrome (CIS; n = 32), and radiologically isolated syndrome (RIS; n = 6); 2) Alzheimer's disease (AD; n = 72), including mild cognitive impairment due to AD (MCI-AD, n = 36) and probable AD dementia (AD-dem; n = 36); 3) Parkinson's disease (PD; n = 30); and 4) other neurological noninflammatory and non-neurodegenerative diseases (OND; n = 30).
Our new NfL ELISA showed a good analytical performance (inter-plate coefficient of variation (CV) < 13%), with no cross-reactivity with neurofilament medium and heavy (NfM and NfH). With respect to the other available ELISAs, CSF NfL showed the same range of values with a strong correlation (r = 0.9984, p < 0.001) between the two methods. CSF NfL levels were significantly higher in MCI-AD/AD-dem and IDD patients as compared with both PD and OND patients. The highest discriminative power was obtained between IDD and OND patients (area under the curve (AUC) 0.87, 95% confidence interval (CI) 0.80-0.95). Within the IDD group, CSF NfL positively correlated with several clinical and radiological disease severity parameters.
These results show a good analytical performance of the new ELISA for quantification of NfL concentrations in the CSF. CSF NfL is confirmed to be a reliable marker in AD and MS, and a disease-severity marker in MS patients.
脑脊液（CSF）神经丝轻链（NfL）是不同神经疾病中神经轴突损伤的可靠标志物，与疾病严重程度相关。迄今为止，所有在人类 CSF 中进行的最新研究都使用了相同的酶联免疫吸附测定法（ELISA）。为了证实 NfL 的大量证据，我们开发了一种新的 ELISA 方法，在此我们介绍了这种新的 CSF NfL ELISA 在不同神经疾病中的性能特征。
我们制备了两种针对 NfL 核心结构域的单克隆抗体（NfL21 和 NfL23），并开发了一种新的夹心 ELISA 方法，我们在以下患者中进行了评估：1）炎症性脱髓鞘疾病（IDD；n=97），包括多发性硬化症（MS；n=59）、临床孤立综合征（CIS；n=32）和放射学孤立综合征（RIS；n=6）；2）阿尔茨海默病（AD；n=72），包括 AD 引起的轻度认知障碍（MCI-AD，n=36）和可能的 AD 痴呆（AD-dem，n=36）；3）帕金森病（PD；n=30）；和 4）其他神经非炎症性和非神经退行性疾病（OND；n=30）。
我们的新型 NfL ELISA 具有良好的分析性能（板间变异系数（CV）<13%），与神经丝中链和重链（NfM 和 NfH）无交叉反应。与其他可用的 ELISA 相比，CSF NfL 的值范围相同，两种方法之间具有很强的相关性（r=0.9984，p<0.001）。MCI-AD/AD-dem 和 IDD 患者的 CSF NfL 水平明显高于 PD 和 OND 患者。IDD 和 OND 患者之间的区分能力最高（曲线下面积（AUC）0.87，95%置信区间（CI）0.80-0.95）。在 IDD 组中，CSF NfL 与多个临床和放射学疾病严重程度参数呈正相关。
这些结果表明，新的 ELISA 具有良好的分析性能，可用于定量 CSF 中的 NfL 浓度。CSF NfL 被证实是 AD 和 MS 中的可靠标志物，也是 MS 患者疾病严重程度的标志物。
