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 vital, they say, in understanding a major medical problem: how atmospheric pollution can trigger dementia.
In recent years, scientists have discovered that air pollution is one of the most pernicious threats to human health and have shown it is involved in causing cancer, heart disease, diabetes, low birthrates, and many health conditions.
Now scientists at the Francis Crick Institute are to look at its involvement in the phenomenon of neurodegeneration through a research project, titled Rapid, which is being funded by the charity Race Against Dementia and will be launched tomorrow.
Rapid will involve scientists examining the exact processes by which tiny polluting particles can lead to dementia, work that could bring an insight into the way air particulates trigger disease in general and also help in the development of new drugs to counter the progress of conditions such as Alzheimer’s disease.
“Air pollution is not generally associated with dementia. However, epidemiologists have found out recently that particulates in the air are actually associated quite firmly 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 tiny particles in the air can have such profound impacts on our brains and use that knowledge to develop new drugs to treat dementia.”
A key type of air pollution consists of suspensions of minuscule fragments of solids and liquid droplets. These are produced from car and truck exhausts, factories, dust, pollen, volcanoes, wildfires and other sources and are known as particulate matter 2.5 or simply PM2.5.
These particulates are less than 2.5 millionths of a metre in diameter – about 30 times finer than a human hair – and are so small they can travel deep into the recesses of the human body. In the case of dementia, PM2.5s are inhaled and are believed to get into the brain through the olfactory bulb, a rounded mass of tissue that sits above the nasal cavity and plays a key role in processing smell 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,” Swanton said.
Exactly how this process unfolds and leads to dementia is not clear, however, and a major aim of the Rapid project will be to reveal the precise process that causes PM2.5s to cause brain tissue to form the clumps that are the hallmark of Alzheimer’s disease.
“We have good evidence that links exposure to PM2.5 particles with brain diseases such as Alzheimer’s and Parkinson’s, but we do not know yet whether these are actually triggering neurodegeneration directly or if they are driving the process that is already occurring in vulnerable individuals,” said Sonia Gandhi, head of the Neurodegeneration Biology Laboratory at the Crick and University College London.
Researchers at the Crick believe one of three different mechanisms is involved in the way air pollution triggers dementia. PM2.5 particles may directly speed up the process by which proteins get clumped together in the brain – and are causing Alzheimer’s.
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Alternatively, it could be that the arrival of particulates interferes with the brain’s ability to clear up clumping. In other words, the PM2.5s are interfering with the body’s cell clearance system and are making it harder to clear other proteins that cause diseases such as Alzheimer’s.
Thirdly, it has been suggested that PM2.5s are being picked up by the brain’s immune cells, called microglia, and could be causing these cells to trigger inflammation which drives the onset of dementia.
The research to find which mechanism is involved in the causation 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 dampen the impact of air pollutants and perhaps one day prevent the effect of the environment on brain diseases,” Gandhi said.
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