Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784743602871599104
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
work_keys_str_mv AT dasshreyasee anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT dewitnele anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT jacobsdirk anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT pijnenburgyolandeal anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT intveldsjorsgjg anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT coppenssalome anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT quagliamilena anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT hirtzchristophe anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT teunissencharlottee anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT vanmecheleneugeen anovelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT dasshreyasee novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT dewitnele novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT jacobsdirk novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT pijnenburgyolandeal novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT intveldsjorsgjg novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT coppenssalome novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT quagliamilena novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT hirtzchristophe novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT teunissencharlottee novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration
AT vanmecheleneugeen novelneurofilamentlightchainelisavalidatedinpatientswithalzheimersdiseasefrontotemporaldementiaandsubjectivecognitivedeclineandtheevaluationofcandidateproteinsforimmunoassaycalibration