New Study Links Air Pollution to Increased Risk of Lewy Body Dementia at Molecular Level

Recent research from Johns Hopkins Medicine has uncovered a potential molecular mechanism connecting air pollution exposure to the development of Lewy body dementia (LBD), a neurodegenerative disorder characterized by abnormal protein buildup in the brain. The study demonstrates how inhaling fine particulate matter (PM2.5)—tiny particles from vehicle emissions, industrial processes, wildfires, and residential burning—can induce the formation of a unique strain of alpha-synuclein protein clumps in mice. These toxic protein aggregates resemble those found in the brains of patients suffering from Lewy body dementia and Parkinson's disease.

The researchers exposed both normal and genetically modified mice, including those lacking alpha-synuclein and mice with mutations linked to early-onset Parkinson’s, to PM2.5 for ten months. They observed that in normal mice, pollution exposure led to brain atrophy, cell death, and cognitive decline—symptoms akin to Lewy body dementia. In contrast, mice without alpha-synuclein showed no significant changes, emphasizing the protein's role in the disease process.

Further, the team identified a novel strain of Lewy bodies formed after pollution exposure, which could serve as a specific target for future therapeutics aimed at slowing disease progression. The study also analyzed hospital records of over 56 million U.S. patients, revealing that increased exposure to PM2.5 correlates with a higher risk of Parkinson’s disease dementia and dementia with Lewy bodies, with each increase in particulate concentration raising the risk by 12-17%. These findings underscore the potential for environmental factors to trigger neurodegeneration.

The investigation extended to different geographic sources of PM2.5, including samples from China, Europe, and the U.S., all resulting in similar brain changes in mice. Gene expression analysis showed parallels between pollution-exposed mice and human Lewy body dementia patients, suggesting that air pollution might influence gene activity related to neurodegeneration.

According to lead researcher Xiaobo Mao, Ph.D., this work not only deepens our understanding of how environmental pollutants can contribute to neurodegenerative diseases but also highlights the importance of controlling pollution exposure. The team aims to identify which specific components in air pollution are responsible for these effects, which could inform public health policies and intervention strategies.

This research adds to the growing recognition that environmental exposure is a significant factor in the development of neurodegenerative disorders, emphasizing the need for environmental health awareness as part of disease prevention strategies. The findings appear in the journal Science and pave the way for future molecular studies targeting pollution-related pathways to mitigate disease risk.