Air Pollution’s Link to Lewy Body Dementia

Fine-particulate air pollution seems to contribute to serious forms of dementia by promoting the formation of toxic protein clumps that damage nerve cells throughout the brain, according to recent research. This type of pollution leads to proteins misfolding into harmful aggregates characteristic of Lewy body dementia, which is the second most prevalent form of dementia after Alzheimer’s.

This discovery carries significant implications for preventing this neurodegenerative disease, affecting millions globally. Researchers are advocating for urgent action to enhance air quality by reducing emissions from industries and vehicles, managing wildfires better, and cutting wood burning in residential areas.

“This is something we can actually change, unlike age or genetics,” explained Dr. Xiaobo Mao, a neurologist at Johns Hopkins University and the study’s lead investigator. “Essentially, clean air policies equate to policies for brain health.”

The research team analyzed hospital records from 56.5 million U.S. patients who were first admitted between 2000 and 2014 with a Lewy body-related neurodegenerative condition. Using the patients’ zip codes, they estimated long-term exposure to PM2.5 pollution—tiny airborne particles smaller than 2.5 thousandths of a millimeter that can reach deep into the lungs and circulate in the bloodstream, brain, and other organs.

The findings indicated that long-term exposure to PM2.5 heightened the risk of developing Lewy body dementia, though it had less of an effect on another neurodegenerative brain illness that isn’t caused by these toxic proteins.

Lewy bodies consist of a protein called alpha-synuclein, which is essential for normal brain function. However, when it misfolds, it can create various harmful clumps that lead to the death of nerve cells and serious diseases as it spreads.

To determine whether air pollution could incite the production of Lewy bodies, researchers exposed mice to PM2.5 pollution every other day for 10 months. Some of the mice were normal, while others were genetically modified to not produce alpha-synuclein. The results were noteworthy: nerve cell death occurred in the normal mice, resulting in cognitive decline and brain shrinkage, whereas the genetically modified mice showed little effect.

Additional tests on the mice showed that PM2.5 pollution encouraged the creation of aggressive and resilient toxic alpha-synuclein clumps resembling Lewy bodies found in humans. Even though this research was conducted on mice, the evidence is considered quite convincing.

“The conclusion seems to imply a strong link between air pollution and Lewy body dementia. We believe it’s a significant driving factor for this kind of dementia,” stated Ted Dawson, a senior author of the study and a professor in the field of neurodegenerative diseases at Johns Hopkins. “It’s essential to make a consistent effort to keep our air clean.”

This work, published in Science, builds on earlier studies that have detected PM2.5 in human brains, with damage associated with Alzheimer’s disease and declines in intelligence.

“Our research holds significant implications for prevention since it identifies air pollution as a modifiable risk factor for Lewy body dementia,” Mao shared. “By lowering overall exposure to air pollution, we could potentially lessen the risk of these debilitating neurodegenerative conditions on a broad scale.”

Last year, scientists at University College London and the Francis Crick Institute initiated a project dubbed Rapid (Role of Air Pollution in Dementia) aimed at exploring the impact of air quality on brain health.

“This is a vital and compelling study that enhances our understanding of how air pollution can fuel neurodegenerative diseases,” noted Prof. Charles Swanton, a co-leader of the Rapid project and deputy clinical director at the Crick. “By linking fine-particulate matter exposure with the biology of Lewy body dementia, we’re bridging the gap between environmental exposure and disease pathology. This work emphasizes the urgent necessity to understand and reduce the impact of air pollution, given its vast and increasing threat to public health.”