Non-productive angiogenesis disassembles A ss plaque-associated blood vessels
| العنوان: | Non-productive angiogenesis disassembles A ss plaque-associated blood vessels |
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| المؤلفون: | Alvarez-Vergara M, Rosales-Nieves A, March-Diaz R, Rodriguez-Perinan G, Lara-Urena N, San Luis C, Sanchez-Garcia M, Martin-Bornez M, Gomez-Galvez P, Vicente-Munuera P, Fernandez-Gomez B, Marchena M, Bullones-Bolanos A, Davila J, Gonzalez-Martinez R, Trillo-Contreras J, Sanchez-Hidalgo A, del Toro R, Scholl F, Herrera E, Trepel M, Korbelin J, Escudero L, Villadiego J, Echevarria M, de Castro F, Gutierrez A, Rabano A, Vitorica J, Pascual A |
| المصدر: | NATURE COMMUNICATIONS r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante instname |
| بيانات النشر: | Nature Publishing Group, 2021. |
| سنة النشر: | 2021 |
| الوصف: | The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around A ss plaques. Here we demonstrate that angiogenesis is started near A ss 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 A ss 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 A ss pathology. We also show that A ss 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. A ss are extracellular deposits relevant in Alzheimer's disease (AD). This study shows that A ss plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=RECOLECTA___::82e8c0df034ef689b954221e24dbe8bcTest https://fundanet.isabial.san.gva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=8650Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.RECOLECTA.....82e8c0df034ef689b954221e24dbe8bc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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