British scientists are about to launch a remarkable research project that will demonstrate how the air we breathe can affect our brains. This work will be essential, they say, to understanding a major medical problem: how atmospheric pollution can cause dementia.
In recent years, scientists have discovered this air pollution is one of the most harmful threats to human health and has been shown to be involved in the cause of cancer, heart disease, diabetes, low birth rates and many health conditions.
Now scientists at the Francis Crick Institute is to look at its involvement in the phenomenon of neurodegeneration through a research project, entitled Rapid, funded by the charity Race Against Dementia and launched tomorrow.
Rapid will involve scientists investigating the precise processes by which small pollutant particles can lead to dementia, work that could provide insight into the way airborne particles cause disease in general and also help develop new drugs to slow the progression of conditions such as e.g. Alzheimer’s disease.
“Air pollution is not generally associated with dementia. However, epidemiologists have recently found out that particles in the air are actually quite strongly associated with the risk of neurodegenerative disease,” said one of the project’s leaders, Prof Charles Swanton, the deputy clinical director of the Crick. “We want to find out exactly how small particles in the air can have such a big impact on our brain and use that knowledge to develop new drugs to treat dementia.”
A key type of air pollution consists of suspensions of tiny fragments of solids and liquid droplets. It is produced from car and truck exhausts, factories, dust, pollen, volcanoes, wildfires and other sources and is known as particulate matter 2.5 or simply PM2.5.
These particles are less than 2.5 millionths of a meter in diameter – about 30 times finer than a human hair – and are so small that they can travel deep into the recesses of the human body. In the case of dementia, PM2.5s are inhaled and are believed to enter the brain through the olfactory bulb, a rounded mass of tissue that sits above the nasal cavity and plays a key role in processing olfactory information.
“In the brain, PM2.5s appear to be taken up by immune cells in the central nervous system and in their wake we think neurodegeneration can then set in,” said Swanton.
However, exactly how this process unfolds and leads to dementia is not clear, and a main aim of the Rapid project will be to reveal the exact process that causes PM2.5’s brain tissue to form the clumps that are the hallmark of Alzheimer’s disease is .
“We have good evidence that exposure to PM2.5 particles is linked to brain diseases such as Alzheimer’s and Parkinson’s, but we do not yet know whether it actually causes neurodegeneration directly or whether it drives the process that is already taking place in vulnerable individuals,” said Sonia Gandhi, head of the Neurodegeneration Biology Laboratory at the Crick and University College London, said.
Researchers at the Crick believe one of three different mechanisms is involved in the way air pollution causes dementia. PM2.5 particles can directly accelerate the process by which proteins are clumped together in the brain – and cause Alzheimer’s disease.
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Alternatively, it could be that the arrival of particles interferes with the brain’s ability to clear clots. In other words, the PM2.5s interfere with the body’s cellular clearance system and make it harder to clear other proteins that cause diseases such as Alzheimer’s.
Third, it has been suggested that PM2.5s are picked up by the brain’s immune cells, called microglia, and can cause these cells to cause inflammation that triggers the onset of dementia.
The research to find out which mechanism is involved in the cause of dementia will focus on in vitro experiments on human stem cells as well as animal models.
“Once we understand those mechanisms in greater detail, we can use that knowledge to develop treatments that will moderate the impact of air pollution and perhaps one day prevent the effect of the environment on brain diseases,” Gandhi said.
