Cedars-Sinai Investigators Find That Particulate Matter in Polluted Air Spurs Brain Changes in Genetically Predisposed Laboratory Mice and Could Speed Onset of the Degenerative Neurological Condition
Investigators from the聽聽at Cedars-Sinai have determined that exposure to polluted air could accelerate development of Alzheimer鈥檚 disease in those with genetic risk factors for the neurodegenerative condition. Their study, conducted in laboratory mice, was published in the peer-reviewed journal聽Neurobiology of Disease.
Keith L. Black, MD
鈥淲e exposed mice to air similar to what we find near major Los Angeles freeways,鈥� said聽, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai, and senior author of the study. 鈥淲e 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.鈥�
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鈥檚 risk of developing it as much as fivefold.
Previous research has shown a correlation between air pollution and Alzheimer鈥檚 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聽, research scientist in the Department of Neurosurgery and the 聽co-senior author of the study.
Tao Sun, PhD
鈥淥ur study covered a wider spectrum of sizes of particulate matter鈥攆rom ultrafine to coarse鈥攖han previous studies did,鈥� Sun said. 鈥淎nd 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鈥檚 disease in genetically predisposed mice.鈥�
Investigators exposed groups of laboratory mice with a genetic predisposition to Alzheimer鈥檚 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鈥檚 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.
鈥淔or 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,鈥� Black said. 鈥淭his could help us prevent those individuals from exposure to a second or third impact, such as air pollution, that could accelerate development of Alzheimer鈥檚 disease.鈥�
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鈥檚 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鈥檚 risk.
鈥淚n this study, we focused on so-called 鈥榝amilial鈥� Alzheimer鈥檚 disease with well-known inherited genetic factors, which accounts for a very small percentage of human Alzheimer鈥檚 patients,鈥� Sun said. 鈥淚n a future study, we plan to focus on the form most often found in humans. It is called sporadic or late-onset Alzheimer鈥檚 disease and involves genetic predisposition that is not inherited and is less understood.鈥澛�
Funding: This study was supported by Health Effects of Air Pollution Foundation grants number BTAP011, BTAP013 and HEAPF015.
