Due to these data supporting an early, presymptomatic increase in cryptic HDGFL2 levels in familial ALS–FTD followed by a decline during symptomatic disease, we analyzed longitudinal CSF samples of both presymptomatic and symptomatic C9orf72 mutation carriers from the NINDS and DIALS cohorts to elucidate the dynamics of cryptic HDGFL2 in CSF (Fig. 5e). Here, HDGFL2 is linked to amyotrophic lateral sclerosis.