To date, it is not fully understood how the aggregation of these proteins drives motor neuron degeneration, but TDP-43, FUS, and SOD1 dysfunction, and C9orf72 mutations have been associated with abnormal RNA metabolism,682,683 impaired DNA repair,684, 685, 686, 687 dysregulated nucleocytoplasmic and axonal transport,688, 689, 690, 691 and compromised mitochondrial function.692, 693, 694, 695 Notably, NFTs and Lewy bodies have also been observed in brain samples of patients with ALS.696. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.