Researchers at UCL and the Francis Crick Institute have embarked on a study to establish a causal link between air pollution and neurodegeneration.
The new project, titled RAPID, will examine the effect of tiny pollutant particles on the body's immune response and subsequent disease development.
Air pollution is a known environmental risk factor for several diseases including cancer, heart disease and neurodegenerative conditions such as Alzheimer's and Parkinson's disease.
Epidemiological studies have also shown an increased proportion of small particle pollutants in the air is associated with increased risk of Alzheimer's and dementia.
However, it remains unclear how this particulate matter alters someone's risk and drives progression of neurodegenerative disease.
Dr Imran Noorani (UCL Queen Square Institute of Neurology and the Crick), said: "We want to tackle a major societal challenge - how the environment, specifically the air we breathe, affects the brain and underpins the onset and progression of dementia. We now have the necessary scientific tools and approaches to address this question."
The RAPID study will build on work led by researchers at UCL and the Crick that revealed how air pollution can cause lung cancer in people who have never smoked. They showed that exposure to tiny pollutant particles causes inflammation in the lungs, which can, in turn, awaken previously dormant mutations and promote the development of cancer*.
Researchers will use a similar approach, focussing on PM2.5, tiny particles that are around 3% of the width of a human hair. They will work to understand if these particulates induce a brain tissue-specific immune response in mice, and what effect this inflammation has on glial cells in the brain.
Glial cells help support, connect and protect the neurons of the central and peripheral nervous systems.
The study will examine how these cells react and if pollution-related inflammation may trigger mechanisms that accelerate characteristics of neurodegeneration, including protein misfolding and aggregation, and damage to neurons.
The team also hope that this work will improve our understanding of how neurodegenerative diseases initiate and develop, opening new opportunities for treatment and prevention.
Professor Sonia Gandhi (UCL Queen Square Institute of Neurology and the Crick) said: "A major gap in our understanding of neurodegenerative diseases is how the environment can trigger or drive pathology. This has been previously a difficult challenge to model and study in depth.
"By discovering the ways in which pollution particles affect the brain, we hope to offer alternative approaches that may ultimately modify the environmental risk of developing brain diseases."
Professor Charles Swanton (UCL Cancer Institute and the Crick) said: "Our ambitious programme adopts a multidisciplinary approach, bringing together expertise from different scientific and clinical areas.
"We are aiming to unravel how genetic risk interacts with our environment. Our work in lung cancer has helped shine a light on how air pollution-induced inflammation drives tumourigenesis (the initial formation of a tumour in the body), and we now want to test the hypothesis that similar inflammatory processes, from the air we breathe, drive the earliest stages of neurodegenerative diseases."
RAPID is part of a new group of projects funded by Race Against Dementia in partnership with Rosetrees, a medical research charity.
*https://www.ucl.ac.uk/news/2022/sep/how-air-pollution-can-cause-lung-cancer-non-smokers-revealed
