This study enabled the determination and validation in independent cohorts of cut-off values expressed as percentile/Z-scores that quantify the deviation of serum NfL level from the control group, adjusted for age and body mass index: in this study, a sNfL Z score above 1.5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3.15, 95% CI 2.35–4.23; p < 0.0001) and in people considered stable with no evidence of disease activity (2.66, 1.08–6.55; p = 0.034; Benkert et al., 2022). This evidence concerns the gene NEFL and multiple sclerosis.