Most people know someone with Alzheimer’s disease. When I was growing up, my grandmother struggled with dementia, and I saw firsthand how difficult that was for our family.
That experience was one reason I became a neurotoxicologist who studies how misshapen proteins and inflammation in the brain can increase over time and cause dementia. While there are ways to treat the symptoms of dementia, researchers are still in search of a cure.
Alzheimer’s disease and other types of dementia are difficult to study, in part because diagnosing the disease early in people is challenging. These diseases typically begin developing two decades prior to most symptoms that would prompt someone to see a clinician. As a result, most researchers use mouse models to test potential therapies for Alzheimer’s.
However, the effects of drugs developed in mice rarely translate to people. In fact, 99% of drugs developed for Alzheimer’s that showed promise in the lab failed in human clinical trials. Brain aging is hard to study in mice, as they do not naturally have the buildup of misshapen proteins seen in dementia. Researchers can genetically modify mice to mimic what happens in a human brain, but it is difficult to mimic every aspect of dementia in one mouse.
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So, scientists have set out to research other animals that naturally experience what happens in the brains of people with Alzheimer’s or dementia. One particular species showing promise as a model to study neurodegenerative disease is the aging dog.
In our newly published research in the journal npj Dementia, my colleagues and I show that the aging dog brain changes in similar ways to a human brain with dementia – highlighting the value of companion dogs as a natural model of neurodegeneration that could help researchers develop better diagnostics and treatments for this disease.
Brain disease in dogs and people
Our work on aging dogs all began with a desire to develop better treatments for dementia. Was there a better way to study the toxic proteins that cause disease than using mice?
Around the same time, I had learned that dogs also get dementia and partnered with my colleague Stephanie McGrath, a veterinary neurologist who studies companion dogs with brain diseases. She was interested in canine cognitive dysfunction syndrome, a condition similar to dementia in people.
Canine cognitive dysfunction affects more than a quarter of dogs over age 12. This type of dementia can be diagnosed through surveys of symptoms that owners see in their dogs. But the abnormal proteins that cause dementia in dogs have not been studied in depth. In order to study canine cognitive dysfunction – and potentially dementia in people – we would need to understand how the brains of companion dogs age.
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Partnering with neuropathologist Caitlin Latimer, my team and I set out to see how the brains of dogs with canine cognitive dysfunction compared to those of people with Alzheimer’s disease. Owners consented to donating brain samples from their old dogs for this study. The dogs had either died naturally or had been euthanized under the direction of their owners, with consultation from their clinical care team, to prevent further decline in their quality of life. Using the same lab analysis methods we used to examine human samples, we found abnormal protein deposits in the same regions of the dog brain as in the brains of people with early dementia.
We then asked whether blood markers commonly seen in Alzheimer’s disease in people undergo similar changes in the dogs with canine cognitive dysfunction. In dogs with high levels of abnormal protein deposits in their brains, we also observed unusually elevated levels of glial fibrillary acidic protein, or GFAP.
Because GFAP is normally found only in the blood during brain injury or disease, it could be a promising biomarker to not only help diagnose dogs with cognitive decline but also provide insights into how dementia progresses in people.
Aging dogs, aging people
There are other ongoing efforts to understand how dogs age.
The Dog Aging Project is a study of more than 50,000 companion dogs over time that seeks to better understand the biological, genetic and environmental factors that influence the aging of the whole body, including the brain.
For example, the Dog Aging Project developed a battery of canine cognitive tests that researchers can use to study early changes in cognition and behavior before the dog shows neurologic symptoms. With this data, researchers can link pathological changes in the brain to behavioral changes.
Better understanding how the canine brain ages can help clarify why some dogs or people get dementia while others do not. Through this work, researchers may be better able to discover new treatments and detect dementia earlier.
Julie Moreno, Associate Professor of Environmental and Radiological Health Sciences, Colorado State University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
