Increased expression of TDP-43 in the skin of amyotrophic lateral sclerosis

Abstract

Transactivation-responsive DNA-binding protein-43 (TDP-43) was identified as a major component of the ubiquitin-positive inclusions in sporadic amyotrophic lateral sclerosis (ALS). However, there has been no study of TDP-43 in ALS skin. The present study investigates TDP-43 in ALS skin. We made a quantitative immunohistochemical study of the expression of TDP-43 in the skin from 15 patients with ALS and 15 control subjects. The proportion of TDP-43-positive (TDP-43+) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.62, P < 0.02) between the proportion and duration of illness in ALS patients. The optical density of TDP-43+ cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.72, P < 0.01) between the immunoreactivity and duration of illness in ALS patients. These data suggest that changes of TDP-43 in ALS skin are likely to be related to the disease process and that metabolic alterations of TDP-43 may take place in the skin of patients with ALS.