The association between ALS and reduced cardiovascular disease is hypothesis-generating, driving novel pathway discovery, and not necessarily secondary to premorbid physical activity.

Those living with the adult neurodegenerative syndrome of amyotrophic lateral sclerosis (ALS) naturally want to understand why. A monogenetic association may be identified in approximately 10% of cases. For the majority, ALS has a polygenetic and environmental ‘multiple hit’ model of pathogenesis, like many cancers, and supported indirectly through analysis of the incidence of ALS in relation to age.1 Neurologists who regularly diagnose those with ALS observe a characteristic syndrome of progressive weakness with strikingly focal symptom onset, but recognise an increasingly complicated phenotypic taxonomy and molecular heterogeneity.2 The causes of ALS may be diverse, and none are yet certain at a cellular level. There is also likely to be a significant pre-symptomatic period.3

A frequent perception concerning the premorbid lifestyle of those with ALS …