A groundbreaking study has uncovered a potential molecular link between air pollution and an increased risk of developing Lewy body dementia. Conducted by a team of researchers, the study builds on over a decade of research connecting exposure to fine particulate air pollution (PM2.5)—originating from industrial activities, residential burning, wildfires, and vehicle exhaust—to a heightened risk of neurodegenerative diseases. Published in the journal Science, these findings contribute to the growing body of evidence suggesting that environmental factors may trigger harmful protein changes in the brain, leading to neurodegeneration.
Understanding Lewy Body Diseases
Lewy body diseases are a group of neurodegenerative disorders characterized by the abnormal accumulation of a protein called alpha-synuclein in the brain. These protein clumps, known as Lewy bodies, are a hallmark of conditions such as Parkinson’s disease and Lewy body dementia. In their latest work, researchers discovered that exposing mice to PM2.5 triggered the formation of abnormal alpha-synuclein clumps. These toxic protein clusters shared structural and disease-related features with those found in the brains of patients suffering from Lewy body dementia.
Scientific Breakthroughs and Expert Insights
“We have identified a novel strain of Lewy bodies formed after exposure to air pollution,” stated Dr. Xiaobo Mao, associate professor of neurology at the Johns Hopkins University School of Medicine. “By defining this strain, we hope to establish a specific target for future drugs aimed at slowing the progression of neurodegenerative diseases marked by Lewy bodies.”
The research began with an analysis of hospital data from 56.5 million U.S. patients admitted between 2000 and 2014 with neurodegenerative diseases. The team focused on patients hospitalized for the first time with Lewy body-related conditions and used ZIP-code-level data to estimate their long-term exposure to PM2.5. According to the study, each interquartile range increase in PM2.5 concentration resulted in a 17 percent higher risk of Parkinson’s disease dementia and a 12 percent higher risk of dementia with Lewy bodies.
“This is among the first human epidemiological studies to zero-in on a dementia subtype linked to Lewy bodies,” said Dr. Xiao Wu, co-first author of the study and assistant professor of Biostatistics at Columbia University Mailman School of Public Health. “The statistical association we uncovered is even stronger than what previous studies found when lumping all Alzheimer’s and related dementias together.”
Exploring Biological Mechanisms
To explore the biological reasons for the association between PM2.5 exposure and Lewy body dementia, researchers conducted experiments on both normal mice and genetically modified mice lacking the alpha-synuclein protein. These mice were exposed to PM2.5 pollution every other day for ten months. “In normal mice, we observed brain atrophy, cell death, and cognitive decline—symptoms similar to those in Lewy body dementia,” explained Dr. Ted Dawson, director of the Johns Hopkins Institute for Cell Engineering. “However, in mice lacking alpha-synuclein, the brain did not exhibit any significant changes.”
The study also included mice with a human gene mutation (hA53T) linked to early-onset Parkinson’s disease. After five months of PM2.5 exposure, these mice developed widespread pockets of alpha-synuclein and experienced cognitive decline. Biophysical and biochemical analyses revealed that these protein clumps were structurally distinct from those that form during natural aging.
Global Implications and Future Research
The researchers sought to determine if air pollution effects varied by location. They found that mice exposed to PM2.5 samples from China, Europe, and the United States exhibited similar brain changes and development of alpha-synuclein pockets, suggesting that the harmful effects of PM2.5 may be consistent across different regions.
Changes in gene expression in the brains of PM2.5-exposed mice were strikingly similar to those found in human patients with Lewy body dementia. This indicates that pollution may not only trigger the build-up of toxic proteins but also drive disease-related gene expression changes in the human brain. “We believe we’ve identified a core molecular link between PM2.5 exposure and the propagation of Lewy body dementia,” Mao emphasized.
While genetic factors play a significant role in neurodegenerative diseases, the scientists suggest that people can potentially control their exposure to pollution. The next goal of the researchers is to identify which specific components in air pollution are driving these effects. Understanding this could help guide public health efforts to reduce harmful exposures and lower the risk of disease.
The study was supported by the National Institutes of Health, the Helis Foundation, the Parkinson’s Foundation, the American Parkinson’s Disease Association, the Freedom Together Foundation, and the Department of Defense. For a full list of co-authors, see the published paper.
