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A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration
Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage; however, the corresponding circulating Nf-L analyte in cerebrospinal fluid (CSF) is poorly characterized. We therefore isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266977/ https://www.ncbi.nlm.nih.gov/pubmed/35806226 http://dx.doi.org/10.3390/ijms23137221 |
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author | Das, Shreyasee Dewit, Nele Jacobs, Dirk Pijnenburg, Yolande A. L. In ‘t Veld, Sjors G. J. G. Coppens, Salomé Quaglia, Milena Hirtz, Christophe Teunissen, Charlotte E. Vanmechelen, Eugeen |
author_facet | Das, Shreyasee Dewit, Nele Jacobs, Dirk Pijnenburg, Yolande A. L. In ‘t Veld, Sjors G. J. G. Coppens, Salomé Quaglia, Milena Hirtz, Christophe Teunissen, Charlotte E. Vanmechelen, Eugeen |
author_sort | Das, Shreyasee |
collection | PubMed |
description | Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage; however, the corresponding circulating Nf-L analyte in cerebrospinal fluid (CSF) is poorly characterized. We therefore isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/mL using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample, and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho = 0.97, p < 0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer’s disease (AD, n = 20) from those with frontotemporal lobe dementia (FTD, n = 20) and control samples with subjective cognitive decline (SCD, n = 20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF. |
format | Online Article Text |
id | pubmed-9266977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92669772022-07-09 A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration Das, Shreyasee Dewit, Nele Jacobs, Dirk Pijnenburg, Yolande A. L. In ‘t Veld, Sjors G. J. G. Coppens, Salomé Quaglia, Milena Hirtz, Christophe Teunissen, Charlotte E. Vanmechelen, Eugeen Int J Mol Sci Article Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage; however, the corresponding circulating Nf-L analyte in cerebrospinal fluid (CSF) is poorly characterized. We therefore isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/mL using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample, and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho = 0.97, p < 0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer’s disease (AD, n = 20) from those with frontotemporal lobe dementia (FTD, n = 20) and control samples with subjective cognitive decline (SCD, n = 20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF. MDPI 2022-06-29 /pmc/articles/PMC9266977/ /pubmed/35806226 http://dx.doi.org/10.3390/ijms23137221 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Das, Shreyasee Dewit, Nele Jacobs, Dirk Pijnenburg, Yolande A. L. In ‘t Veld, Sjors G. J. G. Coppens, Salomé Quaglia, Milena Hirtz, Christophe Teunissen, Charlotte E. Vanmechelen, Eugeen A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration |
title | A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration |
title_full | A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration |
title_fullStr | A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration |
title_full_unstemmed | A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration |
title_short | A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration |
title_sort | novel neurofilament light chain elisa validated in patients with alzheimer’s disease, frontotemporal dementia, and subjective cognitive decline, and the evaluation of candidate proteins for immunoassay calibration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266977/ https://www.ncbi.nlm.nih.gov/pubmed/35806226 http://dx.doi.org/10.3390/ijms23137221 |
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