First, ALS may spread contiguously or non-contiguously following a ‘domino-prion-like’ propagation between neighboring neurons in a cell autonomous or non-cell autonomous manner, mutant SOD1 and normal TDP-43 can undergo a seeded aggregation similar to prions(Münch et al., 2011), and initiate the disease cascade that may lead to synaptic dysfunction and cell death. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.