Our aim was to answer relevant questions related to neurofilament light chain (NfL) as a marker for axonal damage.

NfL is an emerging blood biomarker in multiple sclerosis (MS) patients.

In a translational approach, we assessed NfL in different preclinical models of experimental autoimmune encephalomyelitis (EAE) and in clinical and MRI data of MS patients.

Predominant expression of NfL in CNS areas prone to inflammation explain high levels in serum and CSF which correlated with EAE disease scores. In 537 patient samples, serum (s)NfL levels revealed temporal relapse-dependent elevation as a sign of acute inflammation. In contrast, achievement of NEDA3 was associated with low NfL levels, irrespective of the underlying therapeutic regimen. Importantly, both sNfL levels elevated beyond the 75th percentile in NEDA3 patients as well as spinal cord lesions allow prediction of further disease development. Moreover, in a cohort of patients with clinically isolated syndrome (CIS) according to the 2010 McDonald criteria, now divided into CIS and MS according to the 2017 McDonald criteria, sNfL levels are capable of distinguishing between new CIS and new MS.

Our findings indicate the relevance of acute inflammation as well as neurodegeneration for sNfL and the importance of this axonal protein which is detectable in both CSF and serum.