Increased total TDP-43 protein levels are also observed in motor cortex and spinal cord tissues as well as the plasma and cerebrospinal fluid (CSF) of ALS patients, which are positively correlated with disease severity and duration [38,39,40,41], suggesting the disruption of TDP-43 homeostasis contributes to TDP-43 proteinopathy and disease development. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.