High resolution ultrasound imaging reveals cardiac and vascular dysfunction in the 3xTG mouse model of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disease. Recent clinical studies have demonstrated that patients with AD exhibit compromised cardiac function. In this study, we investigated whether the 3x‐Tg mouse model of AD also presents with cardiovascular dysfunction. This model develops age‐related neuropathology including plaques and tangles, synaptic dysfunction, and amyloid‐beta deposits by six months. In vivo cardiovascular function, determined by echocardiography, was performed in seven‐month‐old male 3xTg mice (n=7) and age‐matched controls (n=8) under isoflurane‐induced anesthesia. While body weight was lower in AD mice compared to control mice, no differences in heart weight were observed between groups. There were no differences in aortic structure, expressed as aortic annulus, sinus of Valsalva, and sinotubular junction between groups. Ventricular dimensions, measured as interventricular septal end diastole and end systole, were also similar between groups. However, ejection fraction was lower in AD mice, whereas early (A) and late (E) atrial ventricular filling velocities, the E/A ratio, and mitral valve deceleration time were increased compared to control mice. In AD mice, pulse wave velocity was increased, which is indicative of increased stiffness and reduced elasticity of the aorta. We observed a significant increase in elastin fiber fragmentation within the media of the aorta, which was associated with overall decreased elastin content and fiber length. Aorta from AD mice also exhibited pronounced medial and adventitial wall thicknesses compared to control mice. Our results provide novel information on structural and functional properties of the heart and aorta in the 3x‐Tg mouse model of AD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.