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
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Abstract
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.
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The 60 clinical CSF samples were measured for NfL, NPTX2, and GluR4 using ELISAs developed and validated in-house.
“The 60 clinical CSF samples were also measured for their concentrations of NfL, NPTX2, and GluR4 using ELISAs developed and validated in-house [25, 26].”
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Research works printed but not linked: 2
- [35]Jacobs D. The Evaluation of Novel Monoclonal Antibodies Targeting Different Forms of Neurofilament Light in Brain and CSF Available online: https://www.researchgate.net/publication/321058365 (accessed on 5 August 2021)
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Das, S., Goossens, J., Jacobs, D., Dewit, N., Pijnenburg, Y. A. L., In ‘t Veld, S. G. J. G., Teunissen, C. E., & Vanmechelen, E. (2023) · Alzheimer's Research & Therapy · doi:10.1186/s13195-023-01212-x · Cited by 50 · see citing works
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- Authors
- Das, S., Dewit, N., Jacobs, D., Pijnenburg, Y. A. L., In ‘t Veld, S. G. J. G., Coppens, S., Quaglia, M., Hirtz, C., Teunissen, C. E., & Vanmechelen, E.
- Affiliations
- ADx NeuroSciences (BE)
- Amsterdam University Medical Centers (NL)
- Department of Clinical Chemistry, Neurochemistry Laboratory, Amsterdam University Medical Centres, Vrije Universiteit, Amsterdam Neuroscience Neurodegeneration, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- LGC (GB)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Vanmechelen, Eugeen
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2022-06-29
- Volume
- 23
- Issue
- 13
- Pages
- 7221
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9266977
- OpenAlex
- W4284994448
- Cited by
- 26
- References
- 38
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 4
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- European Union’s Horizon 2020 research (860197)
- innovation program Marie Curie ITN ‘MIRIADE’ (860197)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neurofilament light chain, cerebrospinal fluid biomarkers, ELISA, monoclonal antibodies, Alzheimer's disease, frontotemporal dementia, subjective cognitive decline, immunoassay calibration, neurodegeneration, axonal injury, diagnostic discrimination
- MeSH terms
- Alzheimer Disease, Animals, Calibration, Cattle, Enzyme-Linked Immunosorbent Assay, Humans, Intermediate Filaments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Neurofilament Proteins, Pick Disease of the Brain, Frontotemporal Dementia, Cognitive Dysfunction
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