The Role of Mitochondrial Superoxide in Alzheimer's Pathology

This project examines the role of antioxidants in mouse models of Alzheimer’s disease. The study will examine the pathophysiological basis of the disease using Magnetic Resonance Imaging (MRI). The outcomes of this project will predict ways of using antioxidant therapy to overcome Alzheimer’s disease.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by deposition of amyloid plaques leading to dementia and memory loss. Oxidative stress is a condition in which reactive oxygen molecules damage cells at a rate greater than the body’s ability to repair that damage. It is also associated with the pathology of Alzheimer’s disease. It is believed that amyloid beta accumulation and oxidative stress are linked; it is not known however which comes first. Our project aims at understanding the role of oxidative stress in AD via using 2 animal models: an AD model and a model that overexpresses an antioxidant enzyme. We are in a unique position not only to study the biochemical and behavioral effects, but also the physiological effects of antioxidants on AD symptoms. We specifically propose to (1) measure the increase of various amyloid beta types in AD mice at several age points and test whether this increase is alleviated by an increased antioxidant protection. (2) measure the integrity of axonal transport (indicative of nerve cell integrity) in AD model mice by in imaging with MRI techniques, and test the effect of antioxidant protection using the same technique. (3) Measure blood flow in the brain of AD model mice and test whether increased antioxidant protection will be beneficial. This aim will be achieved using specialized MRI imaging. The results of this study are extremely important to identify novel targets for the design and use of pharmacological antioxidant agents for the treatment of AD.