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

阿尔茨海默病和其他痴呆症给社会带来了越来越大的负担，据估计 580万美国人患有阿尔茨海默氏症。阿尔茨海默病进展的主要障碍 研究缺乏合适的动物模型，这些动物模型(1)显示出类似于 这些基因见于阿尔茨海默病患者，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一无二地捕捉到了这两个特征。 狗老化项目(DAP)是一个由调查人员组成的联盟，他们的共同目标是了解 伴犬的生物衰老过程，包括年龄相关的认知变化和痴呆，通过 健康促进干预措施的大规模纵向研究和临床评价。多过 最终将有50,000只伴侣犬登记在DAP Pack中，详细的主人调查信息 每年收集，包括诊断犬类疾病的黄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“精密小组”正在进行大量的研究 更深入，包括全基因组测序、兽医审查的电子病历(VEMR)、 和年度评估，包括体检、临床化学、血液表观基因组、血清代谢组和 粪便微生物群。我们建议协同利用DAP的基础设施来创建一个无与伦比的 和独一无二的资源，用于研究同伴狗的阿尔茨海默氏样疾病。 为了实现这一目标，我们将(1)招募200只患有ccd的狗加入一个“ccd精密小组”，该小组将 在高分辨率下与认知正常DAP精确组并行研究，包括 血清AD标志物如AB42、Tau和过度磷酸化Tau的丰度评估，(2) 定量评估100名阿尔茨海默病患者的蛋白质组学和神经病理学特征 犬只自然寿命的终结者，以及(3)创建大型犬类数据和生物标本 以支持未来在伴侣犬身上进行阿尔茨海默氏样疾病的研究。 我们预计，该项目的成功完成不仅将在类似AD的平台上创建丰富的数据集 但也将促使其他研究人员进行大量后续研究。这是我们的希望 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.