Alzheimer's-like pathology features in brains of rabbits with inflamed aortic atherosclerotic plaques

• Main Author: Diamse, Matthew Rey
• Other Authors: Hamilton, James A.
• Language: en_US
• Published: 2019
• Subjects: Medical imaging
• Online Access: https://hdl.handle.net/2144/36540

With the continual growth of the average age of the population and the global rise in obesity, it is important to investigate age related cognitive decline and its many related risk factors. Alzheimer’s Disease is the most common cause of dementia and has been linked to another inflammation-associated disease, atherosclerosis. In our lab’s recent findings, we have demonstrated this mechanistic link between inflammation and atherosclerosis with specialized pro-resolving mediators, such as lipoxin and resolvin found in Omega-3 fatty acids. Here we investigated the viability of our rabbit model of atherosclerosis as a model of Alzheimer’s Disease, in an effort to eventually test the impact of inflammation resolution as a treatment to AD. We developed and optimized an MRI protocol as a way to demonstrate and quantify the effect of vascular inflammation on a brain ex vivo in first a murine model of arterial stiffness. We then applied the refined protocol for use on our rabbit model of atherosclerosis. The mouse brains induced with arterial stiffness showed a significant increase of cerebral microbleeds (indicators of cerebral amyloid angiopathy). Some of the rabbit brains used for this study were found to be preserved for too long but found good images in recently harvested and perfused rabbit brains. While the our findings are currently inconclusive, this thesis proposes a novel method for investigating the mechanistic and synergistic link between inflammation, atherosclerosis, and Alzheimer’s Disease.