Development of Cognitive and Physical Activity Biomarkers for a Companion Dog Model of Alzheimer's Disease

尽管经过数十年的研究，目前还没有任何治疗或干预措施可以预防或逆转这种疾病

Despite decades of research, there are currently no treatments or interventions that can prevent or reverse the course of Alzheimer's disease. Model systems approaches provide a powerful opportunity for preclinical in vivo studies in organisms with relatively fast life histories. However, current models rely largely on laboratory populations of transgenic mice, with notable limitations for translation to humans. Recently, companion dogs have been recognized as a valuable model in aging research because they share many important features with humans, including the same living environments, disease risks and burdens, patterns of actuarial aging, and access to a sophisticated health care system. Dogs also spontaneously develop age-related cognitive impairments along with neuropathology resembling that seen in Alzheimer's disease, making them a potentially powerful model system for Alzheimer's disease research. Although laboratory studies have made progress using dogs as a model for Alzheimer's disease, current methods for assessing cognitive impairments in aging dogs rely on specialized equipment and labor-intensive protocols that are not easily employed outside laboratory settings, limiting our ability to capitalize on the unique benefits of a companion dog model. Thus, there is an urgent need for validated measures and biomarkers focused on cognitive and physical impairments associated with Alzheimer's disease which can be implemented in diverse study designs with companion dogs. We will develop a set of neuropsychiatric tests and physical activity biomarkers that can be used as early indicators, diagnostic tools, and outcome measures in a companion dog model of Alzheimer's disease. Specifically, we will 1) adapt current laboratory neuropsychological tests for economical and scalable implementation with companion dogs, 2) develop short-form cognitive assessments which can be completed by citizen scientists, and 3) develop physical activity biomarkers in dogs, based on measures that predict Alzheimer's disease risk and severity in humans. By integrating these measures with the Dog Aging Project – a nationwide study of aging in 10,000+ companion dogs – we will lay the groundwork for future large-scale research developing a companion dog model of Alzheimer's disease. The measures developed in this proposal will provide key Alzheimer's disease-related endpoints for existing studies in the Dog Aging Project, such as the Test of Rapamycin in Aging Dogs – which implements a veterinary clinical trial of Rapamycin – a promising therapeutic for Alzheimer's disease. Following the development of these measures, researchers will be well positioned to investigate diverse hypotheses about endogenous and exogenous factors contributing to cognitive impairments and dementia, in a model with strong potential for translation to humans.