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

阿尔茨海默病伴侣犬模型认知和身体活动生物标志物的开发

基本信息

批准号：
10118482
负责人：
Daniel Edward Promislow
金额：
$ 41.46万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10118482
关键词：
Accelerometer Address Age-associated memory impairment Aging Algorithms Alzheimer like pathology Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease risk Alzheimer&apos s disease therapeutic Animal Hospitals Animals Biological Biological Assay Biological Markers Biological Models Canis familiaris Clinical Trials Cognition Cognitive Cognitive aging Cohort Studies Companions Day Care Dementia Development Diagnostic Disease Endogenous Factors Environment Equipment Exogenous Factors Fractals Funding Future Genetic Health care facility Healthcare Systems Home environment Human Impaired cognition Impairment Intervention Laboratories Laboratory Study Learning Link Longitudinal Studies Measures Memory Methods Modeling Neuropsychological Tests Neuropsychology Organism Outcome Outcome Measure Pattern Physical activity Play Population Positioning Attribute Privatization Problem Solving Procedures Process Property Protocols documentation Public Health Publications Research Research Design Research Personnel Risk Role Sampling Scientist Senile Plaques Severity of illness Sirolimus System Testing Time Training Transgenic Mice United States National Institutes of Health age effect age related base burden of illness citizen science cognitive development cognitive testing computerized design disorder risk executive function flexibility in vivo innovation life history neuropathology neuropsychiatry novel pre-clinical prevent tool translation to humans web app

项目摘要

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.

尽管经过了数十年的研究，目前还没有任何治疗或干预措施可以预防或逆转这种情况模型系统方法为临床前体内研究提供了强大的机会。对生命史相对较快的生物体的研究然而，当前的模型很大程度上依赖于实验室。转基因小鼠群体，在转化为人类方面存在显着局限性，最近，伴侣狗。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、精算老龄化模式，以及获得先进的医疗保健系统的机会狗也会自发地发展与年龄相关的认知能力。阿尔茨海默病中出现的损伤以及神经病理学的重新组装，使它们成为潜在的疾病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实验室外不易使用的专用设备和劳动密集型方案设置，限制了我们利用伴侣犬模型的独特优势的能力。迫切需要针对相关认知和身体损伤的有效措施和生物标志物阿尔茨海默氏病可以在与伴侣犬一起的不同研究设计中实施。我们将开发一套神经精神测试和身体活动生物标志物，可以尽早使用阿尔茨海默病伴侣犬模型的指标、诊断工具和结果测量。具体来说，我们将 1）调整当前的实验室神经心理学测试，以实现经济且可扩展的目的与伴侣犬一起实施，2）制定简短的认知评估，可以通过以下方式完成公民科学家，以及3）根据预测的措施开发狗的身体活动生物标志物通过将这些措施与狗衰老项目相结合，了解人类阿尔茨海默病的风险和严重程度。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。将为狗衰老项目的现有研究提供与阿尔茨海默病相关的关键终点，例如雷帕霉素在老年犬中的测试——实施了雷帕霉素的兽医临床试验——一个有希望的随着这些措施的发展，研究人员将能够很好地治疗阿尔茨海默病。旨在研究有关内源性和外源性因素的不同假设损伤和痴呆症，该模型具有很强的转化为人类的潜力。