The consistent correlation with disease progression rate, as compared with the inconsistent associations with anatomical burden of disease, represents the most important feature of NFL as CSF or blood biomarker for ALS apart from its diagnostic potential: indeed, it indicates that NFL levels reflect the rate of degeneration of the motor system (determining the release of NFL from the axons of diseased motor neurons) rather than its spatial extent and can therefore be considered as an index of the biological aggressiveness of the disease (Verde et al., 2019b). Here, NEFL is linked to amyotrophic lateral sclerosis.