Phospho-tau changes in the human CA1 during Alzheimer's disease progression

Despite extensive studies regarding tau phosphorylation progression in both human Alzheimer's disease cases and animal models, the molecular and structural changes responsible for neurofibrillary tangle development are still not well understood. Here, by using the antibodies AT100 (recognizes t...

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Detalles Bibliográficos
Autores: Regalado-Reyes, M., Furcila, Diana, Hernández, Félix, Ávila, Jesús, DeFelipe, Javier, León-Espinosa, G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/207459
Acceso en línea:http://hdl.handle.net/10261/207459
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
hippocampus
AT100
Neurofibrillary tangles
pS396
tau phosphorylation
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spelling Phospho-tau changes in the human CA1 during Alzheimer's disease progressionRegalado-Reyes, M.Furcila, DianaHernández, FélixÁvila, JesúsDeFelipe, JavierLeón-Espinosa, G.Alzheimer’s diseasehippocampusAT100Neurofibrillary tanglespS396tau phosphorylationDespite extensive studies regarding tau phosphorylation progression in both human Alzheimer's disease cases and animal models, the molecular and structural changes responsible for neurofibrillary tangle development are still not well understood. Here, by using the antibodies AT100 (recognizes tau protein phosphorylated at Thr212 and Ser214 in the proline-rich region) and pS396 (recognizes tau protein phosphorylated at serine residue 396 in the C-terminal region), we examined phospho-tau immunostaining in neurons from the hippocampal CA1 region of 21 human cases with tau pathology ranging from Braak stage I to VI. Our results indicate that the AT100/pS396 ratio decreases in CA1 in accordance with the severity of the disease, along with its colocalization. We therefore propose the AT100/pS396 ratio as a new tool to analyze the tau pathology progression. Our findings also suggest a conformational modification in tau protein that may cause the disappearance of the AT100 epitope in the late stages of tau pathology, which may play a role in the toxic tangle aggregation. Thus, this study provides new insights underlying the stages for the formation of neurofibrillary tangles in Alzheimer's disease.This work was supported by grants from the following entities: the Spanish Ministerio de Ciencia, Innovación y Universidades (Grants SAF 2015-66603-P and Cajal Blue Brain Project, Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland to JDF and Grant BFU 2016-77885-P to JA and FH), Comunidad de Madrid (S2017/BMD-3700) to JA and FH, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain, CB06/05/0066) and the Alzheimer’s Association (ZEN-15-321663) to JDF.IOS PressMinisterio de Ciencia, Innovación y Universidades (España)Cajal Blue BrainComunidad de MadridCentro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)Alzheimer's AssociationConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/207459reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-66603-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-77885-Phttp://dx.doi.org/10.3233/JAD-181263Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2074592026-05-22T06:33:51Z
dc.title.none.fl_str_mv Phospho-tau changes in the human CA1 during Alzheimer's disease progression
title Phospho-tau changes in the human CA1 during Alzheimer's disease progression
spellingShingle Phospho-tau changes in the human CA1 during Alzheimer's disease progression
Regalado-Reyes, M.
Alzheimer’s disease
hippocampus
AT100
Neurofibrillary tangles
pS396
tau phosphorylation
title_short Phospho-tau changes in the human CA1 during Alzheimer's disease progression
title_full Phospho-tau changes in the human CA1 during Alzheimer's disease progression
title_fullStr Phospho-tau changes in the human CA1 during Alzheimer's disease progression
title_full_unstemmed Phospho-tau changes in the human CA1 during Alzheimer's disease progression
title_sort Phospho-tau changes in the human CA1 during Alzheimer's disease progression
dc.creator.none.fl_str_mv Regalado-Reyes, M.
Furcila, Diana
Hernández, Félix
Ávila, Jesús
DeFelipe, Javier
León-Espinosa, G.
author Regalado-Reyes, M.
author_facet Regalado-Reyes, M.
Furcila, Diana
Hernández, Félix
Ávila, Jesús
DeFelipe, Javier
León-Espinosa, G.
author_role author
author2 Furcila, Diana
Hernández, Félix
Ávila, Jesús
DeFelipe, Javier
León-Espinosa, G.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Cajal Blue Brain
Comunidad de Madrid
Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
Alzheimer's Association
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Alzheimer’s disease
hippocampus
AT100
Neurofibrillary tangles
pS396
tau phosphorylation
topic Alzheimer’s disease
hippocampus
AT100
Neurofibrillary tangles
pS396
tau phosphorylation
description Despite extensive studies regarding tau phosphorylation progression in both human Alzheimer's disease cases and animal models, the molecular and structural changes responsible for neurofibrillary tangle development are still not well understood. Here, by using the antibodies AT100 (recognizes tau protein phosphorylated at Thr212 and Ser214 in the proline-rich region) and pS396 (recognizes tau protein phosphorylated at serine residue 396 in the C-terminal region), we examined phospho-tau immunostaining in neurons from the hippocampal CA1 region of 21 human cases with tau pathology ranging from Braak stage I to VI. Our results indicate that the AT100/pS396 ratio decreases in CA1 in accordance with the severity of the disease, along with its colocalization. We therefore propose the AT100/pS396 ratio as a new tool to analyze the tau pathology progression. Our findings also suggest a conformational modification in tau protein that may cause the disappearance of the AT100 epitope in the late stages of tau pathology, which may play a role in the toxic tangle aggregation. Thus, this study provides new insights underlying the stages for the formation of neurofibrillary tangles in Alzheimer's disease.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/207459
url http://hdl.handle.net/10261/207459
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-66603-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-77885-P
http://dx.doi.org/10.3233/JAD-181263
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv IOS Press
publisher.none.fl_str_mv IOS Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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