Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. A common characteristic of ALS pathology is cytoplasmic inclusions primarily composed of transactive response DNA-binding protein of 43 kDa (TDP-43). Production of TDP-43 in the central nervous system is strictly regulated, but it is not known whether this is also true in the skin of ALS patients. We found a gradual but significant reduction in epidermal TDP-43 mRNA expression with illness progression in ALS patients with upper-limb onset. However, the immunoblotting analysis revealed more TDP-43 protein in the skin of patients with upper-limb onset than of those with other onsets. There was no correlation between the TDP-43 mRNA expression and protein levels, indicating that the mechanism of TDP-43 autoregulation in the patients' skin gradually failed. ALS diagnosis depends on clinical signs and electrophysiological findings, making early diagnosis difficult. TDP-43, as quantified by immunoblot analysis of biopsied skin, is a potential new biomarker of ALS.