Cerebral blood flow in elastin haploinsufficient and 3xTg-AD mice.

Artery structural properties and Alzheimer's disease (AD) pathology are individually associated with impaired cerebrovascular function; however, the interaction of these factors is unclear. Furthermore, while elastin haploinsufficient ( ) mice are known to have impaired cerebrovascular function, sex differences for this effect have not been previously studied. To answer these questions, we crossed middle-aged and old mice with 3xTg-AD mice. We measured cerebral blood flow (CBF) using arterial spin labeling MRI at rest and during hypercapnia to calculate cerebrovascular reactivity (CVR). We also assessed neuroinflammation by microglia and astrocyte cell counts. We found that mice had lower resting blood flow rate in the cerebral cortex compared with mice, but mice had an intact hypercapnic response, resulting in better CVR compared with in hippocampus. Sex did not impact resting blood flow or CVR. 3xTg-AD mice had a lower resting CBF than non-AD mice, and there was an interaction between genotype and AD mutations on CVR, such that x 3xTg-AD mice had the poorest hippocampal CVR of all groups. Glia cell counts were highly dependent on brain region, with having more microglia but fewer astrocytes, while 3xTg-AD having higher both microglia and astrocytes. While sex also impacted glial cell counts, we found no interactions between sex and genotype. Our results demonstrate that elastin haploinsufficiency and AD mutations individually result in lower resting CBF, and the combination of these leads to impaired CVR.