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

Suzuki M, Mikami H, Watanabe T, Yamano T, Yamazaki T, Nomura M, Yasui K, Ishikawa H, Ono S. Increased expression of TDP‐43 in the skin of amyotrophic lateral sclerosis. Acta Neurol Scand: 2010: 122: 367–372. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – Transactivation‐responsive DNA‐binding protein‐43 (TDP‐43) was indentified 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. Materials and methods – We made a quantitative immunohistochemical study of the expression of TDP‐43 in the skin from 15 patients with ALS and 15 control subjects. Results – 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. Conclusions – 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.