Characterization and Validation of Two Recently Created Sheep Models of Alzheimer’s Disease in Preparation for Use as a Preclinical Pharmaceutical Testing Model

One of the challenges when developing treatments is finding a model system to test them in. Good model systems increase the likelihood that the treatments will be successful in human clinical trials, which are logistically challenging, long and expensive. To this end, our group and international collaborators have made two sheep models of Alzheimer’s disease (AD). These animals have been engineered to develop AD in a way that is identical to the natural disease process. Sheep naturally develop the brain changes seen in AD, because the genes responsible are very similar to humans. To accelerate this process, we have altered a single gene in each model to create the same mutation found in humans who develop early-onset forms of AD. Both of our sheep models show the expected blood changes, confirming that they are indeed models of AD. Our aim is to undertake robust measurements of AD progression on a larger number of animals from both lines to establish a baseline for the use of these models for pharmaceutical testing. We also will produce a cohort of animals carrying both mutations aiming to accelerate the disease process for more rapid treatment testing. Lastly, we also plan to test what happens to disease progression by decreasing the expression of a key gene involved in amyloid beta production, as a potential therapeutic avenue. Once characterized, these sheep will be made available for pharmaceutical preclinical testing and to the wider scientific community for the study of AD.