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TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients

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...

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Autores principales: Rubio, Miguel A., Herrando-Grabulosa, Mireia, Velasco, Roser, Blasco, Israel, Povedano, Monica, Navarro, Xavier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773870/
https://www.ncbi.nlm.nih.gov/pubmed/35053327
http://dx.doi.org/10.3390/cells11020209
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author Rubio, Miguel A.
Herrando-Grabulosa, Mireia
Velasco, Roser
Blasco, Israel
Povedano, Monica
Navarro, Xavier
author_facet Rubio, Miguel A.
Herrando-Grabulosa, Mireia
Velasco, Roser
Blasco, Israel
Povedano, Monica
Navarro, Xavier
author_sort Rubio, Miguel A.
collection PubMed
description 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.
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spelling pubmed-87738702022-01-21 TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients Rubio, Miguel A. Herrando-Grabulosa, Mireia Velasco, Roser Blasco, Israel Povedano, Monica Navarro, Xavier Cells Article 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. MDPI 2022-01-08 /pmc/articles/PMC8773870/ /pubmed/35053327 http://dx.doi.org/10.3390/cells11020209 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rubio, Miguel A.
Herrando-Grabulosa, Mireia
Velasco, Roser
Blasco, Israel
Povedano, Monica
Navarro, Xavier
TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title_full TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title_fullStr TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title_full_unstemmed TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title_short TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title_sort tdp-43 cytoplasmic translocation in the skin fibroblasts of als patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773870/
https://www.ncbi.nlm.nih.gov/pubmed/35053327
http://dx.doi.org/10.3390/cells11020209
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