Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus

Muñoz-Castro, Clara; Mejías-Ortega, Marina; Sánchez-Mejias, Elisabeth; Navarro, Victoria; Trujillo-Estrada, Laura; Jiménez-Reyes, Sebastián; García-León, Juan Antonio; Fernández-Valenzuela, Juan J.; Sánchez-Mico, María V.; Romero-Molina, Carmen; Moreno-González, Inés; Baglietto-Vargas, David; Vizuete, Marisa; Gutiérrez, Antonia; Vitorica, Javier

Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, p...

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Autores:	Muñoz-Castro, Clara, Mejías-Ortega, Marina, Sánchez-Mejias, Elisabeth, Navarro, Victoria, Trujillo-Estrada, Laura, Jiménez-Reyes, Sebastián, García-León, Juan Antonio, Fernández-Valenzuela, Juan J., Sánchez-Mico, María V., Romero-Molina, Carmen, Moreno-González, Inés, Baglietto-Vargas, David, Vizuete, Marisa, Gutiérrez, Antonia, Vitorica, Javier
Tipo de recurso:	conjunto de datos
Fecha de publicación:	2023
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/351962
Acceso en línea:	http://hdl.handle.net/10261/351962
Access Level:	acceso abierto
Palabra clave:	Alzheimer’s disease Myeloid cells Microglia Brain infiltration Human hippocampus Amyloid plaques

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dc.title.none.fl_str_mv	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
title	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
spellingShingle	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus Muñoz-Castro, Clara Alzheimer’s disease Myeloid cells Microglia Brain infiltration Human hippocampus Amyloid plaques
title_short	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
title_full	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
title_fullStr	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
title_full_unstemmed	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
title_sort	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
dc.creator.none.fl_str_mv	Muñoz-Castro, Clara Mejías-Ortega, Marina Sánchez-Mejias, Elisabeth Navarro, Victoria Trujillo-Estrada, Laura Jiménez-Reyes, Sebastián García-León, Juan Antonio Fernández-Valenzuela, Juan J. Sánchez-Mico, María V. Romero-Molina, Carmen Moreno-González, Inés Baglietto-Vargas, David Vizuete, Marisa Gutiérrez, Antonia Vitorica, Javier
author	Muñoz-Castro, Clara
author_facet	Muñoz-Castro, Clara Mejías-Ortega, Marina Sánchez-Mejias, Elisabeth Navarro, Victoria Trujillo-Estrada, Laura Jiménez-Reyes, Sebastián García-León, Juan Antonio Fernández-Valenzuela, Juan J. Sánchez-Mico, María V. Romero-Molina, Carmen Moreno-González, Inés Baglietto-Vargas, David Vizuete, Marisa Gutiérrez, Antonia Vitorica, Javier
author_role	author
author2	Mejías-Ortega, Marina Sánchez-Mejias, Elisabeth Navarro, Victoria Trujillo-Estrada, Laura Jiménez-Reyes, Sebastián García-León, Juan Antonio Fernández-Valenzuela, Juan J. Sánchez-Mico, María V. Romero-Molina, Carmen Moreno-González, Inés Baglietto-Vargas, David Vizuete, Marisa Gutiérrez, Antonia Vitorica, Javier
author2_role	author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Instituto de Salud Carlos III European Commission Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) Junta de Andalucía Universidad de Málaga Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	Alzheimer’s disease Myeloid cells Microglia Brain infiltration Human hippocampus Amyloid plaques
topic	Alzheimer’s disease Myeloid cells Microglia Brain infiltration Human hippocampus Amyloid plaques
description	© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
publishDate	2023
dc.date.none.fl_str_mv	2023 2024 2024
dc.type.none.fl_str_mv	info:eu-repo/semantics/dataset http://purl.org/coar/resource_type/c_ddb1
format	dataset
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/351962
url	http://hdl.handle.net/10261/351962
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# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01556 info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00914 info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01557 info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00915 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-108911RA-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107090RA-I00 info:eu-repo/grantAgreement/AEI//RYC-2017-21879 Muñoz-Castro, Clara; Mejías-Ortega, Marina; Sánchez-Mejias, Elisabeth; Navarro, Victoria; Trujillo-Estrada, Laura; Jiménez, Sebastián; García-León, Juan Antonio; Fernández-Valenzuela, Juan J.; Sánchez-Mico, María V.; Romero-Molina, Carmen; Moreno-González, Inés; Baglietto-Vargas, David; Vizuete, Marisa; Gutiérrez, Antonia; Vitorica, Javier. Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus. https://doi.org/10.1186/s40478-023-01530-z. http://hdl.handle.net/10261/351956 https://doi.org/10.1186/s40478-023-01530-z Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
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dc.publisher.none.fl_str_mv	BioMed Central
publisher.none.fl_str_mv	BioMed Central
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
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repository.mail.fl_str_mv
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spelling	Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampusMuñoz-Castro, ClaraMejías-Ortega, MarinaSánchez-Mejias, ElisabethNavarro, VictoriaTrujillo-Estrada, LauraJiménez-Reyes, SebastiánGarcía-León, Juan AntonioFernández-Valenzuela, Juan J.Sánchez-Mico, María V.Romero-Molina, CarmenMoreno-González, InésBaglietto-Vargas, DavidVizuete, MarisaGutiérrez, AntoniaVitorica, JavierAlzheimer’s diseaseMyeloid cellsMicrogliaBrain infiltrationHuman hippocampusAmyloid plaques© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Additional figures (S1-S7) and tables (S1-S2).Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of the CNS and the pathogenesis of Alzheimer's disease (AD). However, the contribution of nonparenchymal or brain-infiltrated myeloid cells to disease progression remains to be demonstrated. Here, we show that monocyte-derived cells (MDC) invade brain parenchyma in advanced stages of AD continuum using transcriptional analysis and immunohistochemical characterization in post-mortem human hippocampus. Our findings demonstrated that a high proportion (60%) of demented Braak V–VI individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes, among which stands the membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes or Cd163. These Cd163-positive MDC invaded the hippocampal parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. Moreover, and most interesting, these invading monocytes infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. However, in aged-matched control individuals with hippocampal amyloid pathology, no signs of MDC brain infiltration or plaque invasion were found. The previously reported microglial degeneration/dysfunction in AD hippocampus could be a key pathological factor inducing MDC recruitment. Our data suggest a clear association between MDC infiltration and endothelial activation which in turn may contribute to damage of the blood brain barrier integrity. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only for microglia but also for the peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying the progression of AD.This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI18/01556 and PI21/00914 (to JV) and PI18/01557 and PI21/00915 (to AG); by Junta de Andalucia Consejería de Economía y Conocimiento through grants US-1262734 and P20-00843 (to JV), UMA18-FEDERJA-211 (to AG) and PI18-RT-2233 (to AG) co-financed by Programa Operativo FEDER 2014-2020; by Spanish Minister of Science and Innovation grant PID2019-108911RA-100 (to DBV), Beatriz Galindo Program BAGAL18/00052 (to DBV), grant PID2019-107090RA-I00 (to IMG) and Ramon y Cajal Program RYC-2017-21879 (to IMG); and by Malaga University grant B-2019_06 (to ESM).Peer reviewedBioMed CentralInstituto de Salud Carlos IIIEuropean CommissionMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Junta de AndalucíaUniversidad de MálagaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/datasethttp://purl.org/coar/resource_type/c_ddb1application/pdfhttp://hdl.handle.net/10261/351962reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01556info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00914info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01557info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00915info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-108911RA-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107090RA-I00info:eu-repo/grantAgreement/AEI//RYC-2017-21879Muñoz-Castro, Clara; Mejías-Ortega, Marina; Sánchez-Mejias, Elisabeth; Navarro, Victoria; Trujillo-Estrada, Laura; Jiménez, Sebastián; García-León, Juan Antonio; Fernández-Valenzuela, Juan J.; Sánchez-Mico, María V.; Romero-Molina, Carmen; Moreno-González, Inés; Baglietto-Vargas, David; Vizuete, Marisa; Gutiérrez, Antonia; Vitorica, Javier. Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus. https://doi.org/10.1186/s40478-023-01530-z. http://hdl.handle.net/10261/351956https://doi.org/10.1186/s40478-023-01530-zSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3519622026-05-22T06:33:51Z
score	15.81155

Additional File for: Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus

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