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

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.