Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis

Abstract

Objective: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the CSF and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in MS.

Methods: sNfL levels were measured in healthy controls (HC, n=254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n=142); (2) longitudinal with repeated serum sampling (n=246, median (IQR) follow-up 3.1 (2.0-4.0) years). We assessed their relation to concurrent clinical, imaging and treatment parameters and to future clinical outcomes.

Results: sNfL levels were higher in both MS cohorts than in HC (p<0.001). We found a strong association between CSF NfL and sNfL (β=0.589, p<0.001). Patients with either brain or spinal (43.4 (25.2-65.3) pg/ml) or both brain and spinal gadolinium enhancing lesions (62.5 (42.7-71.4) pg/ml) had higher sNfL than those without (29.6 (20.9-41.8) pg/ml; β=1.461, p=0.005 and β=1.902, p=0.002 respectively). sNfL was independently associated with EDSS assessments (β=1.105, p<0.001) and presence of relapses (β=1.430, p<0.001). sNfL levels were lower under disease modifying treatment (β=0.818, p=0.003). Patients with sNfL levels above the 80^th, 90^th, 95^th, 97.5^th and 99^th HC based percentiles had higher risk of relapses (97.5^th percentile: IRR=1.94, 95%CI=1.21-3.10, p=0.006) and EDSS worsening (97.5^th percentile: OR=2.41, 95%CI=1.07-5.42, p=0.034).

Interpretation: These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. This article is protected by copyright. All rights reserved.

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