Air pollutants linked to increased risk of Lewy body dementia

Science Editorial, Sep 4 (EFE).- Lewy body diseases are a group of neurodegenerative disorders characterized by the abnormal accumulation of a protein in the brain. Now, an association study and experiments in mice have found a relationship and a possible molecular connection between air pollution and an increased risk of developing them.

Behind the research are experts from Johns Hopkins Medicine and Columbia University in the United States. These findings add to a growing body of evidence indicating how environmental factors could trigger harmful protein changes in the brain that lead to neurodegeneration.

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

The study, published Thursday in Science, is based on a decade of research linking exposure to fine particulate matter (PM2.5) air pollution—from industrial activity, residential burning, wildfires, and vehicle exhaust fumes—with an increased risk of developing these diseases.

The research began with an analysis of hospital data on 56.5 million U.S. patients admitted between 2000 and 2014 with neurodegenerative diseases, according to a statement from Johns Hopkins Medicine.

The team focused on those admitted for the first time with Lewy body-related conditions and used their postcode data to estimate their long-term exposure to PM2.5.

It found that each interquartile range increase in PM2.5 concentration in these areas resulted in a 17% increased risk of Parkinson's dementia and a 12% increased risk of Lewy body dementia.

This statistical association is stronger than that found in previous studies when grouping Alzheimer's and related dementia cases, the authors say.

To explore the biological reason for this link, Xiaobo Mao's team exposed both normal mice and genetically modified mice lacking the alpha-synuclein protein to PM2.5 pollution every two days for a period of ten months.

"In normal subjects, we observed brain atrophy, cell death, and cognitive decline, symptoms similar to those of Lewy body dementia," explains Ted Dawson. "However, in those lacking alpha-synuclein, the brain showed no significant changes."

They then studied mice with a human genetic mutation (hA53T) linked to early-onset Parkinson's. After five months of exposure to PM2.5, the animals developed widespread pockets of alpha-synuclein and experienced cognitive decline.

Observed by biophysical and biochemical analysis, these protein accumulations were structurally distinct from those that form during natural aging.

The researchers also found that mice exposed to separate samples of PM2.5 from China, Europe, and the United States exhibited similar brain changes and the development of alpha-synuclein accumulations.

Furthermore, they say that changes in gene expression in the brains of mice exposed to PM2.5 were strikingly similar to those seen in humans with Lewy body dementia.

"We have identified a new strain of Lewy bodies that forms after exposure to air pollution," Mao summarizes. "By defining this strain, we hope to establish a specific target for future drugs aimed at slowing the progression of neurodegenerative diseases characterized by these."