Amyotrophic lateral sclerosis (ALS) is an intractable neurological disease. Aging is a risk factor for the accumulation of TDP-43 (transduction responsive region DNA-binding protein of 43kDa) in the motor cortex. TDP-43 is a protein that tends to accumulate in increasing amounts, and the amount is strictly controlled by the splicing of TDP-43. Through cell experiments and analysis of human brain tissue, researchers at Brain Research Institute, Niigata University, led by Akihiro Sugai, M.D., Ph.D., have found that methylation of TDP-43 DNA is involved in the background of motor cortex involvement with aging in ALS