Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease, Frontotemporal Dementia, Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration

Shreyasee Das
ORCID logo ,
Nele Dewit
,
Dirk Jacobs
,
Yolande A.L. Pijnenburg
,
Sjors G.J.G. In 't Veld
,
Salomé Coppens
,
Milena Quaglia
,
Christophe Hirtz
,
Charlotte E Teunissen
ORCID logo ,
Eugeen J.M. Vanmechelen
* ORCID logo
Version 1 : Received: 6 May 2022 / Approved: 9 May 2022 / Online: 9 May 2022 (10:14:52 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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. Int. J. Mol. Sci. 2022, 23, 7221. 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. 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. Int. J. Mol. Sci. 2022, 23, 7221.

Abstract

Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage, however the corresponding circulating Nf-L analyte in 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 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.

Keywords

Neurofilament-light; biomarker; immunoassay; ELISA; calibrator

Subject

Biology and Life Sciences, Aging

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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