Article
Non-productive angiogenesis disassembles Aß plaque-associated blood vessels
Author/s | Álvarez Vergara, Maria I.
Rosales Nieves, Alicia E. March Díaz, Rosana Rocío Rodríguez Perinan, Guiomar Lara Ureña, Nieves Ortega de San Luis, Clara Sánchez García, Manuel A. Martín Bornez, Miguel Gómez Gálvez, Pedro Vicente Munuera, Pablo Fernández Gómez, Beatriz Marchena, Miguel Ángel |
Department | Universidad de Sevilla. Departamento de Biología Celular |
Publication Date | 2021 |
Deposit Date | 2021-06-14 |
Published in |
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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 ... 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. |
Funding agencies | Instituto de Salud Carlos III Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas |
Project ID. | SAF2012‐ 33816
SAF2015‐ 6411 1‐ R RTI2018-096629- B-100 SAF2017-90794- REDT PIE13/ 0004 P12‐ CTS‐ 213 8 P12‐ CTS‐ 2232 PI18/01556 PI18/01557 20141431 CB06/05/ 0094 |
Citation | Álvarez Vergara, M.I., Rosales Nieves, A.E., March Díaz, R.R., Rodríguez Perinan, G., Lara Ureña, N., Ortega de San Luis, C.,...,Marchena, M.Á. (2021). Non-productive angiogenesis disassembles Aß plaque-associated blood vessels. Nature Communications, 12 (1), 3098. |
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