Development of a Non-Transgenic Animal Model of Alzheimer's Disease

The Woman’s Board of Northwestern Memorial Hospital and the Eleanor Wood-Prince Grants Initiative are dedicated, among other purposes, to the support and advancement of leading-edge treatments and breakthrough discoveries, including translational research. This proposal requests funding to support a pilot study to gather data requested by an NIH study section that reviewed a new RO1 application that William Klein, John Disterhoft, Daniele Procissi, and myself submitted to test the hypothesis that diabetes and high cholesterol are two different etiologies that contribute to Alzheimer’s-like pathology and cognitive impairments in the rabbit. The proposal is innovative in three important ways: 1) it uses the rabbit instead of the more common murine species (because rabbits have the same amino acid sequence as humans do for amyloid), 2) it proposes that effective treatments for Alzheimer’s disease will ultimately be determined by the etiology of the disease, and 3) we will test the effectiveness and diagnostic capabilities of a newly characterized antibody-nanoprobe complex that binds to amyloid related pathology and is visible with magnetic resonance imaging. Positive results from the proposed experiments would validate the two models and remedy the major criticism of the study section that reviewed our application. An investment of $25,000 from the Eleanor Wood-Prince grants initiative could well lead to funding from the NIH to carry out our full proposal that requests five years of funding at approximately $500,000 per year in direct costs.