Alterations in Cardiovascular Parameters in 5xFAD Murine Model

Abstract

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure cerebral arterial stiffness. Our results showed that while 5xFAD mice exhibited significant differences in ejection time, pulse pressure, and Tei index, many other cardiovascular and cerebral parameters were not different. Despite reports that amyloid plaque deposition begins at an early age of 1.5 months in 5xFAD mice, our results did not indicate significant cardiovascular changes. Studies to elucidate cardiovascular and cerebrovascular parametric changes should be done at later ages where the underlying changes are more profound.

Keywords: 5xFAD; alzheimer's disease; cardiovascular disease; pulse wave velocity.

Figure 1

General parameters in wild‐type and 5xFAD mice. (A,A′) Body weight, (B,B′) aortic cross‐sectional area, and (C,C′) heart rate (HR) in male and female mice. Data are mean ± SEM (n = 5–10/group). *p < 0.05, **p < 0.01, ****p < 0.0001, ns = not significant by unpaired t‐test.

Figure 2

Aortic flow velocity parameters. (A,A′) Peak aortic outflow velocity, (B,B′) mean aortic flow velocity, (C,C′) aortic stroke distance, and (D,D′) aortic ejection time in male and female mice. Data are mean ± SEM (n = 5–10/group). *p < 0.05, **p < 0.01, ****p < 0.0001, ns = not significant by unpaired t‐test.

Figure 3

Aortic blood pressure parameters. (A,A′) Systolic blood pressure (SBP), (B,B′) diastolic blood pressure (DBP), (C,C′) mean blood pressure (MBP), (D,D′) pulse pressure, and (E,E′) rate pressure product (RPP = HR × SBP) in male and female mice. Data are mean ± SEM (n = 5–10/group). *p < 0.05, **p < 0.01, ****p < 0.0001, ns = not significant by unpaired t‐test.

Figure 4

Mitral flow velocity parameters. (A,A′) Mitral peak‐early flow velocity (E wave), (B,B′) isovolumic contraction time (IVCT), (C,C′) isovolumic relaxation time (IVRT), and (D,D′) myocardial performance index (Tei index). Data are mean ± SEM (n = 5–10/group). *p < 0.05, **p < 0.01, ****p < 0.0001, ns = not significant by unpaired t‐test.