A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation.
A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation.
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DOI：
10.1186/s13195-018-0339-1
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发表时间：
2018-01-23
期刊：
影响因子：
--
通讯作者：
Blennow K
中科院分区：
文献类型：
--
作者：
Gaetani L;Höglund K;Parnetti L;Pujol-Calderon F;Becker B;Eusebi P;Sarchielli P;Calabresi P;Di Filippo M;Zetterberg H;Blennow K
脑脊液（CSF）神经丝光（NfL）是不同神经系统疾病中与疾病严重程度相关的神经轴突损伤的可靠标志物。到目前为止，最近在人脑脊液中进行的所有研究都使用了相同的酶联免疫吸附试验（ELISA）。为了证实NfL的大量证据，我们开发了一种新的ELISA方法，在这里我们介绍了这种新的ELISA在不同神经系统疾病中检测CSF NfL的性能特征。我们生产了两种针对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）和放射孤立综合征（RIS, n = 6）；2)阿尔茨海默病（AD, n = 72），包括AD所致轻度认知障碍（MCI-AD, n = 36）和可能的AD痴呆（AD-dem, n = 36）；3)帕金森病（PD, n = 30）；4)其他神经系统非炎性和非神经退行性疾病（OND; n = 30）。新型NfL ELISA具有良好的分析性能（板间变异系数< 13%），与神经丝介质和重质（NfM和NfH）无交叉反应性。与其他可用的elisa相比，CSF NfL的取值范围相同，两种方法之间具有很强的相关性（r = 0.9984, p < 0.001）。与PD和OND患者相比，MCI-AD/AD-dem和IDD患者的CSF NfL水平明显更高。IDD和OND患者的鉴别能力最高（曲线下面积（AUC） 0.87, 95%可信区间（CI） 0.80-0.95）。在IDD组中，脑脊液NfL与几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定量CSF中NfL浓度具有良好的分析性能。CSF NfL被证实是AD和MS的可靠标志物，也是MS患者疾病严重程度的标志物。
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.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
DOI：
10.1089/15368590252917647
发表时间：
2002-02-01
期刊：
HYBRIDOMA AND HYBRIDOMICS
影响因子：
--
作者：
Norgren, N;Karlsson, JE;Stigbrand, T
通讯作者：
Stigbrand, T
影响因子：
9.9
作者：
Arrambide G;Espejo C;Eixarch H;Villar LM;Alvarez-Cermeño JC;Picón C;Kuhle J;Disanto G;Kappos L;Sastre-Garriga J;Pareto D;Simon E;Comabella M;Río J;Nos C;Tur C;Castilló J;Vidal-Jordana A;Galán I;Arévalo MJ;Auger C;Rovira A;Montalban X;Tintore M
通讯作者：
Tintore M
DOI：
10.1038/nrn3921
发表时间：
2015-08
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Lun MP;Monuki ES;Lehtinen MK
通讯作者：
Lehtinen MK
影响因子：
11
作者：
Disanto, Giulio;Adiutori, Rocco;Ramagopalan, Sreeram V.
通讯作者：
Ramagopalan, Sreeram V.