| First Author | Alvarez-Vergara MI | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3098 |
| PubMed ID | 34035282 | Mgi Jnum | J:314716 |
| Mgi Id | MGI:6713967 | Doi | 10.1038/s41467-021-23337-z |
| Citation | Alvarez-Vergara MI, et al. (2021) Non-productive angiogenesis disassembles Ass plaque-associated blood vessels. Nat Commun 12(1):3098 |
| abstractText | 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. |
