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A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation

BACKGROUND: 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 con...

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Autores principales: Gaetani, Lorenzo, Höglund, Kina, Parnetti, Lucilla, Pujol-Calderon, Fani, Becker, Bruno, Eusebi, Paolo, Sarchielli, Paola, Calabresi, Paolo, Di Filippo, Massimiliano, Zetterberg, Henrik, Blennow, Kaj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389166/
https://www.ncbi.nlm.nih.gov/pubmed/29370869
http://dx.doi.org/10.1186/s13195-018-0339-1
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author Gaetani, Lorenzo
Höglund, Kina
Parnetti, Lucilla
Pujol-Calderon, Fani
Becker, Bruno
Eusebi, Paolo
Sarchielli, Paola
Calabresi, Paolo
Di Filippo, Massimiliano
Zetterberg, Henrik
Blennow, Kaj
author_facet Gaetani, Lorenzo
Höglund, Kina
Parnetti, Lucilla
Pujol-Calderon, Fani
Becker, Bruno
Eusebi, Paolo
Sarchielli, Paola
Calabresi, Paolo
Di Filippo, Massimiliano
Zetterberg, Henrik
Blennow, Kaj
author_sort Gaetani, Lorenzo
collection PubMed
description BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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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spelling pubmed-63891662019-03-19 A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation Gaetani, Lorenzo Höglund, Kina Parnetti, Lucilla Pujol-Calderon, Fani Becker, Bruno Eusebi, Paolo Sarchielli, Paola Calabresi, Paolo Di Filippo, Massimiliano Zetterberg, Henrik Blennow, Kaj Alzheimers Res Ther Research BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2018-01-23 /pmc/articles/PMC6389166/ /pubmed/29370869 http://dx.doi.org/10.1186/s13195-018-0339-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Gaetani, Lorenzo
Höglund, Kina
Parnetti, Lucilla
Pujol-Calderon, Fani
Becker, Bruno
Eusebi, Paolo
Sarchielli, Paola
Calabresi, Paolo
Di Filippo, Massimiliano
Zetterberg, Henrik
Blennow, Kaj
A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
title A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
title_full A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
title_fullStr A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
title_full_unstemmed A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
title_short A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
title_sort new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389166/
https://www.ncbi.nlm.nih.gov/pubmed/29370869
http://dx.doi.org/10.1186/s13195-018-0339-1
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