A possible link has been found between pollution and the risk of developing a type of dementia.

Researchers at Johns Hopkins Medicine have led a study that identifies a possible molecular connection between air pollution and an increased risk of developing Lewy body dementia .

The findings add to a growing body of evidence indicating how environmental factors can trigger detrimental changes in brain proteins , leading to neurodegeneration .

Lewy body diseases are a group of neurodegenerative disorders characterized by the abnormal accumulation of the protein alpha-synuclein in the brain. These aggregates, known as Lewy bodies, are a hallmark of diseases such as Parkinson's disease and Lewy body dementia.

The study, published in Science , builds on a decade of research linking exposure to fine particulate matter (PM2.5) — from industrial activities, residential combustion, wildfires and vehicle emissions — with an increased risk of developing these diseases, said lead researcher Xiaobo Mao, a professor of neurology at Johns Hopkins University and a member of the Johns Hopkins Institute for Cell Engineering.

In this new study, Mao's team found that exposing mice to PM2.5 induced the formation of abnormal alpha-synuclein aggregates . These toxic clumps shared structural and pathological features with those observed in the brains of patients with Lewy body dementia.

“We have identified a new strain of Lewy bodies formed after exposure to air pollution,” says Mao. “By defining this strain, we hope to establish a specific target for future drugs that slow the progression of neurodegenerative diseases marked by Lewy bodies.”

The research began with an analysis of hospital data from 56.5 million US patients admitted between 2000 and 2014 with neurodegenerative diseases.

The team focused on first-time hospitalizations with Lewy body-related conditions and used ZIP codes to estimate their long-term exposure to PM2.5. The scientists found that each increase in the interquartile range of PM2.5 concentrations in these areas was associated with a 17% increased risk of Parkinson's dementia and a 12% increased risk of Lewy body dementia.

“The statistical association we found is even stronger than that observed in previous studies that grouped all Alzheimer’s-related dementias together—highlighting Lewy body formation as a potentially key pathway worthy of further biological investigation,” said Xiao Wu, co-senior author and professor of biostatistics at the Columbia University Mailman School of Public Health.

“We hope to encourage other researchers to conduct epidemiological and molecular studies focused on Lewy body dementia subtypes,” Wu adds.

To explore the biological basis for this association between PM2.5 and Lewy body dementia, the researchers exposed both normal mice and genetically modified mice lacking the alpha-synuclein protein to PM2.5 pollution every other day for 10 months.

“In normal mice, we observed brain atrophy, cell death, and cognitive decline—symptoms similar to those of Lewy body dementia,” explains Ted Dawson, director of the Cell Engineering Institute at Johns Hopkins Medicine. “But in mice lacking alpha-synuclein, the brain showed no significant changes.”

The researchers also studied mice with a human genetic mutation (hA53T) associated with early-onset Parkinson's . After five months of exposure to PM2.5, these mice developed widespread accumulations of alpha-synuclein and showed cognitive impairment.

The team also wanted to determine whether the effects of pollution varied by geographic region. They found that mice exposed to PM2.5 samples from China, Europe, and the United States exhibited similar brain changes and developed accumulations of alpha-synuclein.

The effects of pollution were similar in samples from different regions, and the brain changes observed in mice were consistent with those in human patients. The study points to a molecular link between PM2.5 exposure and Lewy body dementia and proposes identifying the most harmful components to guide public health measures.