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

开发私人伴侣犬作为阿尔茨海默病的模型

基本信息

批准号：
10478219
负责人：
CHRISTOPHER DIRK KEENE
金额：
$ 127.43万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10478219
关键词：
Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer’s disease biomarker American Amyloid beta-42 Amyloid beta-Protein Animal Model Animals Architecture Autopsy Biological Aging Biological Preservation Biological Specimen Banks Blood Body Size Brain Brain Pathology Canis familiaris Catalogs Clinical Clinical Chemistry Cognition Cognitive Companions Comparative Study Computerized Medical Record DNA Data Data Set Dementia Deposition Diagnosis Disease Disease Marker Enrollment Environment Family Caregiver Family member Foundations Future Genetic Goals Gold Health Health Status Heterogeneity Human Immunohistochemistry Impaired cognition Individual Infrastructure Institutes Intervention Life Experience Link Longitudinal Studies Mass Spectrum Analysis Measures Molecular Pathologic Patients Persons Population Control Process Proteomics Questionnaires Research Research Personnel Resolution Resources Sampling Secure Serum Serum Markers Societies Surveys Testing Text Time Tissues Universities Veterinarians Veterinary Medicine age related age related cognitive change biobank cloud based cognitive function cognitive testing cohort college data repository data warehouse design end of life epigenome expectation fecal microbiome genome sequencing healthspan hyperphosphorylated tau interest longitudinal analysis metabolome molecular phenotype neuropathology recruit repository research clinical testing research study sex tau Proteins whole genome

项目摘要

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.

阿尔茨海默氏病和其他痴呆症代表着越来越多的社会燃烧，估计 580万美国人患有阿尔茨海默氏病。阿尔茨海默氏病进展的主要障碍研究缺乏合适的动物模型，（1）显示病理标志和临床特征类似那些在阿尔茨海默氏病的患者中看到的，（2）具有相似的遗传和环境异质性给人。私有的同伴狗独特地捕获了这两个功能。狗老化项目（DAP）是调查人员的财团，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症，在同伴中通过大规模的纵向研究和推定健康启动干预措施的临床评估。多于 50,000只伴侣狗最终将入学DAP包，为此详细的所有者调查信息每年收集，包括用于诊断犬的金标准认知评估问卷认知功能障碍（CCD）。一个高分辨率的“精度小组”由1,000只狗进行了研究更大的深度，包括完整的基因组测序，兽医评论的电子病历（VEMRS），和年度评估，包括体格检查，临床化学，血液基因组，血清代谢组和粪便微生物组。我们建议通过协同利用DAP的基础架构来创建无与伦比的以及一种研究同伴狗中的阿尔茨海默氏病疾病的一种资源。为了实现这一目标，我们将（1）将200只用CCD招募到一个“ CCD Precision组”，这将与认知上正常的DAP精确组并联，以高分辨率进行研究评估AB42，TAU和高磷酸化的AD标记的血清丰度，（2）定量评估来自100的大脑中阿尔茨海默氏病的蛋白质组学和神经病理学标志达到自然生命尽头的伴侣狗，以及（3）创建一个大型犬类数据和生物循环系统存储库支持同伴狗中对阿尔茨海默氏病的未来研究。我们预计该项目的成功完成不仅会在类似广告的情况下创建丰富的数据集伴侣犬的疾病，但也会刺激其他研究者的大量后续研究。这是我们的希望并期望这些资源将对阿尔茨海默氏病研究产生重大影响未来。