Fine-particulate air pollution can drive devastating forms of dementia by triggering the formation of toxic clumps of protein that destroy nerve cells as they spread through the brain, research suggests.
Exposure to the airborne particles causes proteins in the brain to misfold into the clumps, which are hallmarks of Lewy body dementia, the second most common form of dementia after Alzheimer’s disease.
The finding has “profound implications” for preventing the neurodegenerative disorder, which affects millions worldwide, with scientists calling for a concerted effort to improve air quality by cutting emissions from industrial activity and vehicle exhausts, improving wildfire management and reducing wood burning in homes.
“Unlike age or genetics, this is something we can change,” said Dr Xiaobo Mao, a neurologist at Johns Hopkins University in the US and the study’s lead investigator. “The most direct implication is that clean air policies are brain health policies.”
The researchers began by analysing hospital records of the 56.5 million US Medicare patients. They looked at those who were admitted for the first time between 2000 and 2014 with the protein damage. Armed with the patients’ zip codes, the scientists estimated their long-term exposure to PM2.5 pollution, airborne particles that are smaller than 2.5 thousandths of a millimetre. These can be inhaled deep into the lungs and are found in the bloodstream, brain and other organs.
They found that long-term exposure to PM2.5 raised the risk of Lewy body dementia, but had less of an impact on rates of another neurodegenerative brain disease that is not driven by the toxic proteins.
Lewy bodies are made from a protein called alpha-synuclein. The protein is crucial for healthy brain functioning, but can misfold in various ways to produce different kinds of harmful Lewy bodies. These can kill nerve cells and cause devastating disease by spreading through the brain.
To see if air pollution could trigger Lewy bodies, the team exposed mice to PM2.5 pollution every other day for 10 months. Some were normal mice, but others were genetically modified to prevent them making alpha-synuclein. The results were striking: in normal mice, nerve cells died off, leading to brain shrinkage and cognitive decline. The genetically modified mice were largely unaffected.
Further work in mice showed that PM2.5 pollution drove the formation of aggressive, resilient and toxic clumps of alpha-synuclein clumps that looked very similar to Lewy bodies in humans. Although the work is in mice, the findings are considered compelling evidence.
“Putting the two together, to me, indicates that there’s a pretty strong association with air pollution causing Lewy body dementia. We think it’s a very important driving factor for dementia,” said Ted Dawson, a senior author on the study and a professor in neurodegenerative diseases at Johns Hopkins. “There needs to be a concerted effort to keep our air clean.”
The work, published in Science, builds on previous studies that have found PM2.5s in people’s brains where damage has been linked to Alzheimer’s disease and reductions in intelligence.
“Our findings have profound implications for prevention because they identify air pollution as a modifiable risk factor for Lewy body dementia,” Mao told the Guardian. “By lowering our collective exposure to air pollution, we can potentially reduce the risk of developing these devastating neurodegenerative conditions on a population-wide scale.”
Last year, researchers at University College London and the Francis Crick Institute in London launched a project called Rapid, for Role of Air Pollution in Dementia, to investigate how the air we breathe may harm the brain.
“This is an important and compelling study that deepens our understanding of how air pollution can drive neurodegenerative disease,” said Prof Charles Swanton, a co-leader of the Rapid project and deputy clinical director at the Crick.
“By linking fine-particulate matter exposure to the biology of Lewy body dementia, it provides a mechanistic bridge between environmental exposure and disease pathology. More broadly, the work underscores the urgent need to understand and mitigate the impact of air pollution on dementia and disease risk more broadly, given its enormous and growing public health burden.”