NEFL and amyotrophic lateral sclerosis: While some studies on patients carrying pathogenic variants in different ALS-related genes only detected differences in Nfs levels when they were compared to familial controls in the early symptomatic phase [27], two other studies by the same authors found an elevation in serum NfL levels in patients with the pathogenic SOD1 A4V2 variant up to 12 months before the onset of manifest symptoms [28] and 2 and 3.5 years in the case of C9ORF72 and FUS, respectively [29].