TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
Rubio, Miguel Ángel (Hospital del Mar (Barcelona, Catalunya))
Herrando-Grabulosa, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Velasco, Roser (Universitat Autònoma de Barcelona. Institut de Neurociències)
Blasco, Israel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Povedano, Monica (Institut d'Investigació Biomèdica de Bellvitge)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2022
Abstract:	Diagnosis of ALS is based on clinical symptoms when motoneuron degeneration is significant. Therefore, new approaches for early diagnosis are needed. We aimed to assess if alterations in appearance and cellular localization of cutaneous TDP-43 may represent a biomarker for ALS. Skin biopsies from 64 subjects were analyzed: 44 ALS patients, 10 healthy controls (HC) and 10 neurological controls (NC) (Parkinson's disease and multiple sclerosis). TDP-43 immunoreactivity in epidermis and dermis was analyzed, as well as the percentage of cells with TDP-43 cytoplasmic localization. We detected a higher amount of TDP-43 in epidermis (p < 0. 001) and in both layers of dermis (p < 0. 001), as well as a higher percentage of TDP-43 cytoplasmic positive cells (p < 0. 001) in the ALS group compared to HC and NC groups. Dermal cells containing TDP-43 were fibroblasts as identified by co-labeling against vimentin. ROC analyses (AUC 0. 867, p < 0. 001; CI 95% 0. 800-0. 935) showed that detection of 24. 1% cells with cytoplasmic TDP-43 positivity in the dermis had 85% sensitivity and 80% specificity for detecting ALS. We have identified significantly increased TDP-43 levels in epidermis and in the cytoplasm of dermal cells of ALS patients. Our findings provide support for the use of TDP-43 in skin biopsies as a potential biomarker.
Grants:	Agencia Estatal de Investigación RTI2018-096386-B-I00 Ministerio de Sanidad y Consumo CB06/05/1105 Ministerio de Economía y Competitividad RD16/0011/0014
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Amyotrophic lateral sclerosis ; Dermis ; Skin biopsy ; TDP-43 ; Biomarker
Published in:	Cells, Vol. 11 (january 2022) , ISSN 2073-4409

DOI: 10.3390/cells11020209
PMID: 35053327

12 p, 1.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles