Effect of aging on cerebrovascular, aortic and cardiac function in hAPOE3 and hAPOE4 male and female mice
Authors: Eckman Delrae , Gusek Brikena , Christensen Ashley , Liu Zi Qian , Vallejo-Elias Johana , Jones T Bucky , Jones Carleton 
Published: May 2023

Alzheimer’s disease (AD) is the most common form of dementia and is the 6th leading cause of death in the US. Growing evidence supports a link between AD and cardiovascular disease (CVD). Variant isoforms of apolipoprotein E (APOE) are risk factors for both AD and CVD. The most common APOE isoform, APOE3, has neutral risk for developing AD, whereas APOE4 increases AD risk. Pathogenic alterations in cardiac- and carotid- artery function are known to contribute to neurodegenerative diseases including AD. In this aging study we characterize cerebrovascular, aortic and cardiac function in the young (3–4-month-old), and aged (18-20-month-old) mice expressing human-ApoE targeted replacement of APOE3 (B6.129P2-Apoetm2(APOE*3)MaeN8) and APOE4 (B6.129P2-Apoetm3(APOE*4)MaeN8) (Taconic Labs). In vivo high-resolution ultrasound imaging was performed to evaluate the structure and function of the heart, aorta, carotid artery (CA), and posterior cerebral artery (PCA) blood flow in young, and aged hAPOE3 and hAPOE4 mice. Results were considered significant at p<0.05. PCA peak flow velocity showed no significant difference in young compared to aged, male, or female hAPOE3 and hAPOE4 groups. CA structure and function were assessed by wall thickness (WT) and pulse wave velocity (PWV) respectively. Our data showed an age-related increase in CA PWV and WT in both male and female hAPOE3 and hAPOE4 groups. An age-relate increase in was also seen in the aortic PWV, an index of aortic stiffness, in both male and female hAPOE3 and hAPOE4 groups. Cardiac output (CO) was significantly increased in aged male hAPOE3 mice compared to young male hAPOE3 and in aged male hAPOE3 compared to aged female hAPOE3. Stroke volume (SV) was significantly increased in the aged male hAPOE3 compared to the young male hAPOE3 group and significantly decreased in aged male hAPOE4 compared to aged male hAPOE3 group. No significant difference was shown in the ejection fraction (EF) between groups, while left ventricular mass (LV mass) showed an age-related increase in male and female hAPOE3, in aged male hAPOE3 compared to aged female hAPOE3 and a significant decrease in aged female hAPOE4 compared to aged female hAPOE3.These results suggest that there are allele, sex and age-related changes in the cardiac, aortic and carotid artery structure and function of these mice that could lead to the development of AD or CVD. ABRC/ADHS18-205211 (DME, CBJ), Arizona Alzheimer's Consortium (funded by the Arizona Department of Health Services, Contract No. CTR040636) and matching funds from Midwestern University (DME), Biomedical Sciences Program (JF, KW, JD, DME), Biomedical Sciences Start-up Funds (DME) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.