Impact of APOE e4 on Aortic Stiffness and Carotid Artery Stiffness in Adults at Risk of Alzheimer’s Disease

The apolipoprotein E e4 allele (APOE e4) is a well-established genetic risk factor for Alzheimer’s disease (AD), associated with increased cerebral amyloid deposition and alterations in cerebrovascular dynamics. Vascular stiffness plays a critical role in cerebral blood flow regulation, potentially exacerbating AD pathology in APOE e4 carriers. Elevated carotid artery stiffness can lead to increased pulse wave transmission, while higher aortic stiffness is associated with lower cerebral perfusion, further elevating the risk of neurodegeneration. Therefore, the purpose of this study was to investigate differences in carotid and aortic stiffness between APOE e4+ and APOE e4- middle-aged adults at risk of AD. We hypothesize that APOE e4+ individuals exhibit higher carotid stiffness and aortic stiffness, potentially contributing to increased risk of AD. A total of 72 participants, aged 63 ± 4 years were recruited, with 30 APOE e4+ (11 males, 19 females) and 42 APOE e4- (14 males, 28 females). After instrumentation in the supine position, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by brachial sphygmomanometry. Aortic stiffness was measured from carotid-to-femoral pulse wave velocity (cfPWV) using applanation tonometry at the carotid and femoral arteries. Carotid artery beta stiffness was measured using B-mode ultrasound imaging combined with simultaneous applanation tonometric-obtained arterial pressure waveforms from the contralateral carotid artery. There were no significant differences between the two groups for blood pressure (APOE e4+ vs. APOE e4-; SBP: 126±16mmHg vs. 125±14mmHg, DBP: 76±7mmHg vs. 75±8mmHg, MAP: 93±9mmHg vs. 91±9mmHg; p>0.05 for all) and cfPWV (APOE e4+: 8.46±1.64m/s vs. APOE e4-: 8.26±1.44m/s; p>0.05). In contrast, carotid artery beta stiffness was significantly greater in APOE e4+ compared with APOE e4- (9.01±2.48au vs. 7.86±2.12au; p<0.05). These results indicate that while blood pressure and aortic stiffness were not different between groups, carotid artery beta stiffness was higher in APOE e4+ adults compared with APOE e4- adults. Our findings suggest an association between APOE e4 genotype and carotid artery stiffness and underscore the importance of vascular health for neurodegenerative risk profiles in genetically susceptible populations. Further research will enhance understanding of the vascular contributions to AD, emphasizing the need for targeted interventions in APOE e4 carriers. Alzheimer’s Association Research Grant #17-499398 and Wisconsin Alzheimer’s Disease Research Center Grant: P30-AG062715. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.