Investigators from the Department of Neurosurgery at Cedars-Sinai have determined that exposure to polluted air could accelerate development of Alzheimer’s disease in those with genetic risk factors for the neurodegenerative condition. Their study, conducted in laboratory mice, was published in the peer-reviewed journal Neurobiology of Disease.

“We exposed mice to air similar to what we find near major Los Angeles freeways,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai, and senior author of the study. “We were surprised by the hundreds of genetic changes we saw in the brains of these mice. Many genes that interfere with learning and memory were turned on. And many genes necessary to maintaining structural support of the brain and maintaining cells that are critical for brain function were turned off.”

The study, which found that coarse airborne particles caused the most pronounced brain changes, could help government agencies prioritize targets for air quality regulation, Black said.

Half of the population has a genetic predisposition to Alzheimer's disease, according to Black. The progressive condition destroys memory and other mental functions, and genetic factors can increase a person’s risk of developing it as much as fivefold.

Previous research has shown a correlation between air pollution and Alzheimer’s disease in humans. And previous studies conducted at Cedars-Sinai found that exposing normal, healthy mice to polluted air caused inflammatory changes in the brain. This study built on that work, said Tao Sun, PhD, research scientist in the Department of Neurosurgery and the  co-senior author of the study.

“Our study covered a wider spectrum of sizes of particulate matter—from ultrafine to coarse—than previous studies did,” Sun said. “And the exposure time we used is significantly longer than in previously published research. It is the first study to show that this exposure accelerated some of the hallmarks of Alzheimer’s disease in genetically predisposed mice.”

Investigators exposed groups of laboratory mice with a genetic predisposition to Alzheimer’s disease to clean, filtered air and to air polluted with ultrafine, fine and coarse particulate matter for three and six months, then looked at the effects on their brains.

Because Alzheimer’s risk is based on a combination of genetic and environmental factors, the knowledge gained in studies such as this one can help improve health outcomes for patients, Black said.

“For people who have genetic risk factors, we will eventually be able to develop biomarkers and tests so that we can assess whether we need to take protective measures,” Black said. “This could help us prevent those individuals from exposure to a second or third impact, such as air pollution, that could accelerate development of Alzheimer’s disease.”

Going forward, the team will examine mice that were exposed to air pollution for a full year, since the exposure to air pollution in the real world is a chronic process. And Black said investigators will look into other factors, including infection and head injury, that could combine with genetic predisposition to accelerate the onset of Alzheimer’s disease.

Sun said investigators are also planning to look into the effects of air pollution on mice that represent a more common type of Alzheimer’s risk.

“In this study, we focused on so-called ‘familial’ Alzheimer’s disease with well-known inherited genetic factors, which accounts for a very small percentage of human Alzheimer’s patients,” Sun said. “In a future study, we plan to focus on the form most often found in humans. It is called sporadic or late-onset Alzheimer’s disease and involves genetic predisposition that is not inherited and is less understood.” 

Funding: This study was supported by Health Effects of Air Pollution Foundation grants number BTAP011, BTAP013 and HEAPF015.