2026-04-29T23:04:22Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/183552024-11-28T14:54:32Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16958
Repisalud
author
Alvarez-Vergara, Maria I.
author
Rosales-Nieves, Alicia E.
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March-Diaz, Rosana
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Rodriguez-Perinan, Guiomar
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Lara-Ureña, Nieves
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Ortega-de San Luis, Clara
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Sanchez-Garcia, Manuel A.
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Martin-Bornez, Miguel
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Gómez-Gálvez, Pedro
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Vicente-Munuera, Pablo
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Fernandez-Gomez, Beatriz
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Marchena, Miguel A.
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Bullones-Bolanos, Andrea S.
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Davila, Jose C.
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Gonzalez-Martinez, Rocio
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Trillo-Contreras, Jose L.
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Sanchez-Hidalgo, Ana C.
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del Toro, Raquel
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Scholl, Francisco G.
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Herrera, Eloisa
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Trepel, Martin
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Körbelin, Jakob
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Escudero, Luis M.
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Villadiego, Javier
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Echevarria, Miriam
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de Castro, Fernando
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Gutierrez, Antonia
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Rábano, Alberto
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Vitorica, Javier
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Pascual, Alberto
authoraffiliation
[Alvarez-Vergara,MI; Rosales-Nieves,AE; March-Diaz,R; Rodriguez-Perinan,G; Lara-Ureña,N; Ortega-de San Luis,C; Sanchez-Garcia,MA; Martin-Bornez,M; Gómez-Gálvez,P; Vicente-Munuera,P; Bullones-Bolanos,AS; Trillo-Contreras,JL; Sanchez-Hidalgo,AC; del Toro,R; Scholl,FG; Escudero,LM; Villadiego,J; Echevarria,M; Vitorica,J; Pascual,A] Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain. [Gómez-Gálvez,P; Vicente-Munuera,P; Escudero,LM] Department of Biología Celular, Universidad de Sevilla. Seville, Spain. [Gómez-Gálvez,P; Vicente-Munuera,P; Davila,JC; Escudero,LM; Villadiego,J; Echevarria,M; Gutierrez,A; Vitorica,J] Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Fernandez-Gomez,B; Marchena,MA; de Castro,F] Grupo de Neurobiología del Desarrollo-GNDe, Instituto Cajal-CSIC, Madrid, Spain. [Marchena,MA] Departamento de Medicina, Facultad de Ciencias, Biomédicas y de la Salud, Universidad Europea de Madrid, Villaviciosa de Odón, Spain. [Davila,JC; Gutierrez,A] Department of Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. [Gonzalez-Martinez,R; Herrera,E] 7 Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Alicante, Spain. [Trillo-Contreras,JL; Sanchez-Hidalgo,AC; del Toro,R; Scholl,FG; Villadiego,J; Echevarria,M] Department of Fisiología Médica y Biofisica, Universidad de Sevilla, Seville, Spain. [del Toro,R] Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain. [Trepel,M] Augsburg Medical Center, Department of Hematology and Oncology, Augsburg, Germany. [Körbelin,J] Section of Pneumology, Department of Oncology, Hematology and Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [Rabano,A] Fundacion CIEN, Madrid, Spain. [Vitorica,J] Department of Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain. [Ortega-de San Luis,L] Present address: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College of Dublin, Dublin, Ireland. [Sanchez-Garcia,MA] Present address: Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK. [Alvarez-Vergara,MI; Rosales-Nieves,AE] These authors contributed equally: Maria I. Alvarez-Vergara, Alicia E. Rosales-Nieves.
2024-02-19T15:28:28Z
2024-02-19T15:28:28Z
2021-05-25
10.1038/s41467-021-23337-z
2041-1723
Nature Communications
http://hdl.handle.net/10668/4516
34035282
http://hdl.handle.net/20.500.12105/18355
The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD.
eng
Alzheimer disease
Brain
Endothelial cells
Presenilins
Péptidos beta-Amiloides
Plaque, amyloid
Blood vessels
Vascular malformations
Angiogenesis
Enfermedad de Alzheimer
Encéfalo
Células endoteliales
Presenilinas
Péptidos beta-amiloides
Placa amiloide
Vasos sanguíneos
Malformaciones vasculares
Non-productive angiogenesis disassembles Aß plaque-associated blood vessels
research article