Developing the Privately Owned Companion Dog as a Model for Alzheimers Disease

阿尔茨海默氏病和其他痴呆症代表了社会日益增加的负担， 5.8数百万美国人患有阿尔茨海默病。阿尔茨海默病进展的主要障碍 研究缺乏合适的动物模型，其（1）显示出类似于 阿尔茨海默病患者中出现的那些，以及（2）具有相似的遗传和环境异质性 对人们来说私人拥有的伴侣狗独特地捕捉到了这两个特征。 狗衰老项目（DAP）是一个研究者联盟，其共同目标是了解 生物衰老过程，包括与年龄相关的认知变化和痴呆，在伴侣犬，通过 大规模的纵向研究和临床评估的假定健康促进干预措施。超过 50，000只伴侣犬最终将被纳入DAP包，其中详细的主人调查信息 每年收集一次，包括诊断犬的金标准认知评估问卷 认知功能障碍（CCD）。一个由1,000只狗组成的高分辨率“精确组”正在被研究， 更深入，包括全基因组测序，兽医审查的电子病历（VEMR）， 以及年度评估，包括体格检查、临床化学、血液表观基因组、血清代谢组，以及 粪便微生物组我们建议协同利用DAP的基础设施， 也是研究伴侣犬类阿尔茨海默病的独一无二的资源。 为了达到这个目标，我们将（1）招募200只CCD狗成为一个“CCD精确组”， 与认知正常的DAP精密组平行进行高分辨率研究，包括 评估AD标志物如Ab 42、Tau和过度磷酸化Tau的血清丰度，（2） 定量评估阿尔茨海默病样疾病的蛋白质组学和神经病理学标志， 伴侣狗谁达到他们的自然生命的尽头，和（3）创建一个大型犬数据和生物标本 库，以支持未来的研究阿尔茨海默氏症样疾病的伴侣狗。 我们预计，该项目的成功完成不仅将创建一个丰富的数据集， 疾病的伴侣狗，但也将刺激许多后续研究的其他研究人员。我们希望 并期望这些资源将对阿尔茨海默病的研究产生重大影响， 未来

Alzheimer’s disease and other dementias represent an increasing burden on society, with an estimated 5.8 million Americans suffering from Alzheimer’s disease. A major barrier to progress in Alzheimer’s disease research is a lack of suitable animal models that (1) show pathological hallmarks and clinical features similar to those seen in patients with Alzheimer’s disease, and (2) have similar genetic and environmental heterogeneity to people. The privately-owned companion dog uniquely captures both of these features. The Dog Aging Project (DAP) is a consortium of investigators with the shared goal of understanding the biological aging process, including age-related cognitive changes and dementia, in companion dogs through large-scale longitudinal study and clinical evaluation of putative healthspan-promoting interventions. More than 50,000 companion dogs will ultimately be enrolled in the DAP Pack, for which detailed owner survey information is collected annually, including the gold standard cognitive assessment questionnaire for diagnosis of canine cognitive dysfunction (CCD). A high-resolution “Precision Group” of 1,000 dogs are being studied in much greater depth, including full genome sequencing, veterinarian-reviewed electronic medical records (VEMRs), and annual assessments including physical exam, clinical chemistry, blood epigenome, serum metabolome, and fecal microbiome. We propose to synergistically leverage the infrastructure of the DAP to create an unparalleled and one-of-a-kind resource for studying Alzheimer’s-like disease in the companion dog. To accomplish this goal, we will (1) recruit 200 dogs with CCD into a “CCD Precision Group” which will be studied at high resolution in parallel with the cognitively normal DAP Precision Group, including assessments of serum abundance of AD markers such as Ab42, Tau, and hyperphosphorylated Tau, (2) quantitatively assess proteomic and neuropathological hallmarks of Alzheimer’s-like disease in brains from 100 companion dogs who reach the end of their natural lives, and (3) create a large canine data and biospecimen repository to support future studies of Alzheimer’s-like disease in companion dogs. We anticipate that successful completion of this project will not only create a rich dataset on AD-like disease in companion dogs, but will also spur numerous follow-on studies by other investigators. It is our hope and expectation that these resources will have a major impact on Alzheimer’s disease research far into the future.