As the neuropathological basis of the ALS-associated propagation patterns in the brain, four neuropathological stages have been defined for ALS, based upon the distribution patterns of phosphorylated 43 kDa TAR DNA-binding protein (101, 102): the sequential protein pathology is spreading initially from the motor neocortex toward the spinal cord and brainstem, followed by spreading to frontal, parietal, and, ultimately, anteromedial temporal lobes. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.