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

尽管进行了数十年的研究，但目前还没有任何治疗或干预措施可以预防或逆转 老年痴呆症的病因模型系统方法为临床前体内研究提供了强大的机会。 在具有相对快速生命史的生物体中进行的研究。然而，目前的模型主要依赖于实验室 转基因小鼠的群体，具有显著的局限性翻译给人类。最近，狗狗们 被认为是衰老研究中的一个有价值的模型，因为它们与 人类，包括相同的生活环境，疾病风险和负担，精算老化模式， 进入先进的医疗保健系统。狗也会自发地发展出与年龄相关的认知能力， 沿着类似于阿尔茨海默病的神经病理学损伤，使其成为潜在的 阿尔茨海默病研究的强大模型系统。尽管实验室研究已经取得了进展， 狗作为阿尔茨海默病的模型，目前评估老年狗认知障碍的方法 依赖于不容易在实验室外使用的专用设备和劳动密集型协议 设置，限制了我们利用伴侣犬模型的独特优势的能力。因此， 迫切需要有效的措施和生物标志物，重点是与认知和身体障碍有关的 这可以在有伴侣狗的各种研究设计中实施。 我们将开发一套神经精神测试和身体活动生物标志物， 指标，诊断工具，并在阿尔茨海默病的伴侣狗模型的结果措施。 具体来说，我们将1）调整目前的实验室神经心理学测试， 与伴侣犬一起实施，2）开发简短的认知评估，可以通过以下方式完成 公民科学家，和3）开发狗的身体活动生物标志物，基于预测的措施， 阿尔茨海默病的风险和严重程度在人类。通过将这些措施与狗老化项目相结合-a 全国范围内对10，000多只伴侣犬的衰老研究-我们将为未来的大规模研究奠定基础 研究开发阿尔茨海默病的伴侣狗模型。本提案中制定的措施 将为狗衰老项目中现有的研究提供关键的阿尔茨海默病相关终点，例如 雷帕霉素在老龄犬中的试验-实施雷帕霉素的兽医临床试验-一个有前途的 治疗阿尔茨海默病的药物随着这些措施的发展，研究人员将很好地 定位于调查各种假设的内源性和外源性因素有助于认知 损伤和痴呆症，在一个具有很强的潜力翻译到人类的模型。

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.