Why Old Dogs Could Teach Alzheimer’s Researchers New Tricks

Most people know someone with Alzheimer’s disease. When I was a child, my grandmother suffered from dementia and I saw firsthand how difficult it was for our family.

This experience is one of the reasons I became a neurotoxicologist who studies how distorted proteins and inflammation in the brain can increase over time and cause dementia. Although there are ways to treat the symptoms of dementia, researchers are still searching for a cure.

Alzheimer’s disease and other types of dementia are difficult to study, in part because it is difficult to diagnose the disease in its early stages. These diseases typically begin to develop two decades before most symptoms that would prompt a person to see a clinician. As a result, most researchers use mouse models to test potential therapies for Alzheimer’s disease.

However, the effects of drugs developed in mice rarely translate to humans. In fact, 99% of drugs developed for Alzheimer’s disease that have shown promise in the laboratory have failed in human clinical trials. Brain aging is difficult to study in mice because they do not naturally exhibit the accumulation of distorted proteins seen in dementia. Researchers can genetically modify mice to mimic what happens in the human brain, but it’s difficult to mimic all aspects of dementia in a single mouse.

So scientists set out to look for other animals that naturally experience what happens in the brains of people with Alzheimer’s disease or dementia. The aging dog is a particular species that appears promising as a model for studying neurodegenerative diseases.

In our research recently published in the journal npj Dementia, my colleagues and I show that the aging dog brain changes in the same way as a human brain with dementia – highlighting the value of pet dogs as a natural model of neurodegeneration that could help researchers develop better diagnostics and treatments for this disease.

Brain Disease in Dogs and Humans

Our work on aging dogs began with a desire to develop better treatments for dementia. Is there a better way to study toxic proteins that cause disease than using mice?

Around the same time, I had learned that dogs also suffered from dementia, and I teamed up with my colleague Stephanie McGrath, a veterinary neurologist who studies pet dogs with brain diseases. She was interested in canine cognitive dysfunction syndrome, a disease similar to dementia in humans.

Canine cognitive dysfunction affects more than a quarter of dogs over 12 years old. This type of dementia can be diagnosed through investigations of the symptoms owners observe in their dogs. But the abnormal proteins responsible for dementia in dogs have not been studied in depth. In order to study canine cognitive dysfunction – and potentially dementia in humans – we would need to understand how the brains of pet dogs age.

In partnership with neuropathologist Caitlin Latimer, my team and I sought to compare the brains of dogs with canine cognitive dysfunction to those of people with Alzheimer’s disease. The owners agreed to donate brain samples from their old dogs for this study. The dogs died naturally or were euthanized at the direction of their owners, in consultation with their clinical care team, to avoid further decline in their quality of life. Using the same laboratory analysis methods used to examine human samples, we found abnormal protein deposits in the same regions of the dog’s brain as in the brains of people with early-onset dementia.

We next asked whether blood markers commonly seen in Alzheimer’s disease in humans undergo similar changes in dogs with canine cognitive dysfunction. In dogs with high levels of abnormal protein deposits in the brain, we also observed unusually high levels of glial fibrillary acidic protein, or GFAP.

Since GFAP is normally only found in the blood during brain injury or disease, it could be a promising biomarker not only to help diagnose dogs suffering from cognitive decline, but also to better understand how dementia progresses in humans.

Aging dogs, aging people

Other efforts are underway to understand how dogs age.

The Dog Aging Project is a study of more than 50,000 pet dogs over time that seeks to better understand the biological, genetic and environmental factors that influence aging of the entire body, including the brain.

For example, the Dog Aging Project has developed a battery of canine cognitive tests that researchers can use to study early cognitive and behavioral changes before the dog shows neurological symptoms. Using this data, researchers can associate pathological changes in the brain with changes in behavior.

Better understanding how the canine brain ages may help understand why some dogs or people suffer from dementia while others do not. With this work, researchers may be better able to discover new treatments and detect dementia earlier.