In the seminal work of Benatar et al. [85], pre-symptomatic carriers of known disease-causing mutations (e.g. SOD1, C9orf72, TARDBP, FUS, VCP) showed rising levels of serum NfL up to 11.6 months before “phenoconversion” (i.e., the onset of motor symptoms typical of ALS). This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.