| First Author | Nortley R | Year | 2019 |
| Journal | Science | Volume | 365 |
| Issue | 6450 | PubMed ID | 31221773 |
| Mgi Jnum | J:277601 | Mgi Id | MGI:6336199 |
| Doi | 10.1126/science.aav9518 | Citation | Nortley R, et al. (2019) Amyloid beta oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes. Science 365(6450) |
| abstractText | Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid beta (Abeta) constricts brain capillaries at pericyte locations. This was caused by Abeta generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by Abeta could potentially reduce energy lack and neurodegeneration in AD. |
