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oai: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

00925njm 22002777a 4500 dc Alvarez-Vergara, Maria I. author Rosales-Nieves, Alicia E. author March-Diaz, Rosana author Rodriguez-Perinan, Guiomar author Lara-Ureña, Nieves author Ortega-de San Luis, Clara author Sanchez-Garcia, Manuel A. author Martin-Bornez, Miguel author Gómez-Gálvez, Pedro author Vicente-Munuera, Pablo author Fernandez-Gomez, Beatriz author Marchena, Miguel A. author Bullones-Bolanos, Andrea S. author Davila, Jose C. author Gonzalez-Martinez, Rocio author Trillo-Contreras, Jose L. author Sanchez-Hidalgo, Ana C. author del Toro, Raquel author Scholl, Francisco G. author Herrera, Eloisa author Trepel, Martin author Körbelin, Jakob author Escudero, Luis M. author Villadiego, Javier author Echevarria, Miriam author de Castro, Fernando author Gutierrez, Antonia author Rábano, Alberto author Vitorica, Javier author Pascual, Alberto author 2021-05-25 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. 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 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