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Title: Non-productive angiogenesis disassembles Aß plaque-associated blood vessels.
Authors: Alvarez-Vergara, Maria I
Rosales-Nieves, Alicia E
March-Diaz, Rosana
Rodriguez-Perinan, Guiomar
Lara-Ureña, Nieves
Ortega-de San Luis, Clara
Sanchez-Garcia, Manuel A
Martin-Bornez, Miguel
Gómez-Gálvez, Pedro
Vicente-Munuera, Pablo
Fernandez-Gomez, Beatriz
Marchena, Miguel A
Bullones-Bolanos, Andrea S
Davila, Jose C
Gonzalez-Martinez, Rocio
Trillo-Contreras, Jose L
Sanchez-Hidalgo, Ana C
Del Toro, Raquel
Scholl, Francisco G
Herrera, Eloisa
Trepel, Martin
Körbelin, Jakob
Escudero, Luis M
Villadiego, Javier
Echevarria, Miriam
de Castro, Fernando
Gutierrez, Antonia
Rabano, Alberto
Vitorica, Javier
Pascual, Alberto
metadata.dc.subject.mesh: Alzheimer Disease
Amyloid beta-Peptides
Blood Vessels
Disease Models, Animal
Endothelial Cells
Gene Expression Profiling
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neovascularization, Pathologic
Plaque, Amyloid
Reverse Transcriptase Polymerase Chain Reaction
Issue Date: 25-May-2021
Abstract: 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.
metadata.dc.identifier.doi: 10.1038/s41467-021-23337-z
Appears in Collections:Producción 2020

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