| First Author | Austin SA | Year | 2020 |
| Journal | J Cereb Blood Flow Metab | Volume | 40 |
| Issue | 2 | Pages | 392-403 |
| PubMed ID | 30614363 | Mgi Jnum | J:327451 |
| Mgi Id | MGI:6884431 | Doi | 10.1177/0271678X18822474 |
| Citation | Austin SA, et al. (2020) Partial loss of endothelial nitric oxide leads to increased cerebrovascular beta amyloid. J Cereb Blood Flow Metab 40(2):392-403 |
| abstractText | Cerebral amyloid angiopathy (CAA) is present in over half of the elderly population and in 80-90% of Alzheimer's disease (AD) patients. CAA is defined by the deposition of beta amyloid (Abeta) in small cerebral arteries and capillaries. Cardiovascular risk factors are associated with an increased incidence of CAA. We utilized 18-month-old endothelial nitric oxide synthase (eNOS) heterozygous knockout ((+/-)) mice, a clinically relevant model of endothelial dysfunction, to examine the role of endothelial nitric oxide (NO) in vascular Abeta accumulation. eNOS(+/-) mice had significantly higher vascular levels of Abeta40 (P < 0.05). Abeta42 was not detected. There was no difference in Abeta in brain tissue. Amyloid precursor protein and beta-site APP cleavage enzyme 1 protein levels were unaltered, while levels of the alpha-secretase enzyme, a disintegrin and metalloproteinase 10, were significantly lower in eNOS (+ /-) microvascular tissue (P < 0.05). Insulin degrading enzyme and low-density lipoprotein receptor-related protein 1 were significantly increased in eNOS(+/-) microvascular tissue, most likely an adaptive response to locally higher Abeta concentrations. Lastly, catalase and CuZn superoxide dismutase were significantly elevated in eNOS(+/-) microvascular tissue (P < 0.05). These data demonstrate decreased availability of endothelial NO leads to increased cerebrovascular concentration of Abeta along with compensatory mechanisms to protect the vasculature. |
