In TAR DNA-binding protein 43kDa (TDP-43)-related ALS (ALS-TDP), upper and lower motor neurons that are distantly connected by the pyramidal tract are affected, showing neuronal loss and TDP-43 aggregation in both areas, resulting in a system degeneration of motor neurons [81,82]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.