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...

Descripción completa

Detalles Bibliográficos
Autores: Rubio, Miguel Ángel|||0000-0003-0735-6854, Herrando-Grabulosa, Mireia|||0000-0002-6685-3220, Velasco, Roser|||0000-0003-3194-9406, Blasco, Israel|||0000-0002-8806-8733, Povedano, Monica, Navarro, X. (Xavier)|||0000-0001-9849-902X
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252211
Acceso en línea:https://ddd.uab.cat/record/252211
https://dx.doi.org/urn:doi:10.3390/cells11020209
Access Level:acceso abierto
Palabra clave:Amyotrophic lateral sclerosis
Dermis
Skin biopsy
TDP-43
Biomarker
id ES_2f84d2cf96d7c6c8b6f4150288ea47d3
oai_identifier_str oai:ddd.uab.cat:252211
network_acronym_str ES
network_name_str España
repository_id_str
spelling TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS PatientsRubio, Miguel Ángel|||0000-0003-0735-6854Herrando-Grabulosa, Mireia|||0000-0002-6685-3220Velasco, Roser|||0000-0003-3194-9406Blasco, Israel|||0000-0002-8806-8733Povedano, MonicaNavarro, X. (Xavier)|||0000-0001-9849-902XAmyotrophic lateral sclerosisDermisSkin biopsyTDP-43BiomarkerDiagnosis 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. 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/252211https://dx.doi.org/urn:doi:10.3390/cells11020209reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-096386-B-I00Ministerio de Sanidad y Consumo https://doi.org/10.13039/501100011033 CB06/05/1105Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0011/0014open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2522112026-06-06T12:50:31Z
dc.title.none.fl_str_mv TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
title TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
spellingShingle TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
Rubio, Miguel Ángel|||0000-0003-0735-6854
Amyotrophic lateral sclerosis
Dermis
Skin biopsy
TDP-43
Biomarker
title_short 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_sort TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
dc.creator.none.fl_str_mv Rubio, Miguel Ángel|||0000-0003-0735-6854
Herrando-Grabulosa, Mireia|||0000-0002-6685-3220
Velasco, Roser|||0000-0003-3194-9406
Blasco, Israel|||0000-0002-8806-8733
Povedano, Monica
Navarro, X. (Xavier)|||0000-0001-9849-902X
author Rubio, Miguel Ángel|||0000-0003-0735-6854
author_facet Rubio, Miguel Ángel|||0000-0003-0735-6854
Herrando-Grabulosa, Mireia|||0000-0002-6685-3220
Velasco, Roser|||0000-0003-3194-9406
Blasco, Israel|||0000-0002-8806-8733
Povedano, Monica
Navarro, X. (Xavier)|||0000-0001-9849-902X
author_role author
author2 Herrando-Grabulosa, Mireia|||0000-0002-6685-3220
Velasco, Roser|||0000-0003-3194-9406
Blasco, Israel|||0000-0002-8806-8733
Povedano, Monica
Navarro, X. (Xavier)|||0000-0001-9849-902X
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Amyotrophic lateral sclerosis
Dermis
Skin biopsy
TDP-43
Biomarker
topic Amyotrophic lateral sclerosis
Dermis
Skin biopsy
TDP-43
Biomarker
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.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/252211
https://dx.doi.org/urn:doi:10.3390/cells11020209
url https://ddd.uab.cat/record/252211
https://dx.doi.org/urn:doi:10.3390/cells11020209
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-096386-B-I00
Ministerio de Sanidad y Consumo https://doi.org/10.13039/501100011033 CB06/05/1105
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0011/0014
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405483298717696
score 15.300719

Similares en LA Referencia