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Historically, ALS was classified as a "sporadic" disease, with only a small percentage linked to inheritance. However, the discovery of causative genes such as SOD1 , C9orf72 , TARDBP , and FUS has blurred the line between sporadic and familial ALS. Current research suggests that ALS is a spectrum disorder, possibly overlapping with Frontotemporal Dementia (FTD), driven by complex gene-environment interactions.
The pathogenesis of ALS is multifactorial. No single mechanism explains all cases, suggesting a convergent pathway where various insults lead to motor neuron death.