Due to the temporal differences between increases in CSF levels of cryptic HDGFL2 and NF subunits, we propose a staging scale whereby the ratio of CSF NfL:cryptic HDGFL2 or pNfH:cryptic HDGFL2 concentrations (ng ml−1) would be <1 during the presymptomatic stage of ALS–FTD and increase to >1 during symptomatic disease (Fig. 5h). This evidence concerns the gene HDGFL2 and amyotrophic lateral sclerosis.