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Abstract

Background:

There is a lack of reliable biomarkers of axonal degeneration. Neurofilaments are promising candidates to fulfil this task. We compared two highly sensitive assays to measure two subunits of the neurofilament protein (neurofilament light (NfL) and neurofilament heavy chain (NfH)).

Methods:

We evaluated the analytical and clinical performance of the UmanDiagnostics NF-light^® enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of a group of 148 patients with clinically isolated syndrome (CIS) or multiple sclerosis (MS), and 72 controls. We compared our results with referring levels of our previously-developed CSF NfH^SMI35 assay.

Results:

Exposure to room temperature (up to 8 days) or repetitive thawing (up to 4 thaws) did not influence measurement of NfL concentrations. Values of NfL were higher in all disease stages of CIS/MS, in comparison to controls (p ≤ 0.001). NfL levels correlated with the Expanded Disability Status Scale (EDSS) score in patients with relapsing disease (r_s = 0.31; p = 0.002), spinal cord relapses and with CSF markers of acute inflammation. The ability of NfL to distinguish patients from controls was greater than that of NfH^SMI35 in both CIS patients (p = 0.001) and all MS stages grouped together (p = 0.035).

Conclusions:

NfL proved to be a stable protein, an important prerequisite for a reliable biomarker, and the NF-light^® ELISA performed better in discriminating patients from controls, compared with the ECL-NfH^SMI35 immunoassay. We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration. Our results further support the role of neurofilaments as a potential surrogate measure for neuroprotective treatment in MS studies.

Keywords

Cerebrospinal fluid multiple sclerosis clinically isolated syndrome neurodegeneration neurofilament neurofilament heavy chain neurofilament light chain relapse disability immunoassay biomarker study design

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A comparative study of CSF neurofilament light and heavy chain protein in MS

Abstract

Background:

Methods:

Results:

Conclusions:

Keywords

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