title: <Original Article>TDP-43 in the skin of amyotrophic lateral sclerosis patients.
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.
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Abe
authors.forename: Takuya
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C000598624:TARDBP protein, human