In recent years it has become apparent that the brain’s immune response has a role to play in the development of dementia. Researchers are yet to fully understand the relationship between blood supply and the brain’s inflammatory response, and the impact these have on nerve cell health. While there has been a flurry of activity to investigate the brain’s immune system in Alzheimer’s, less is known about this process in vascular dementia. This study will tease apart the details of how our immune system responds to reduced blood flow and give new insights into nerve cell damage in both Alzheimer’s and vascular dementia – the two most common causes of dementia.
Changes in blood flow to the brain can mean that the cells don’t receive all the nutrients they require to function well. This can have damaging consequences for nerve cell health, affecting a person’s memory and thinking skills. In addition to this, disrupted blood flow in the brain may also trigger the brain’s inflammatory response. Part of this inflammatory response is regulated by TREM2, an Alzheimer’s risk gene that was identified by an Alzheimer’s Research UK-funded study in 2012.
By probing the role of TREM2 in the inflammatory response caused by a reduction in blood flow, Dr McColl and his student, are gaining new insights into the nerve cell damage seen in vascular dementia – a vital step in uncovering new approaches to tackle the disease.
Through this project, the team aims to unravel the role of TREM2 in the interplay between disrupted blood flow and memory and thinking difficulties. They will use mice to investigate the impact of reduced blood flow in the brain, using a range of techniques to look at the immune response. The team is particularly interested in specialised cells called microglia, which are key players in the brain’s inflammatory response to damage. TREM2 plays an important role in regulating the activity of these cells. To look at microglia in more detail, the team will tease out these specialised cells from other cells in the brain. They will employ specialised techniques to compare the impact of disrupted blood flow when TREM2 is and isn’t present. As well as looking at biological changes in the brain, such as how a lack of TREM2 affects nerve cell health and communication, the student will also look at memory changes in the mice. This will help the team unravel the contribution of TREM2 to both the immune response, and to memory and thinking difficulties.
This project will help the researchers uncover more about the inflammatory response triggered by reduced blood flow, investigating the knock-on consequences for nerve cell health and the impact that this may have on memory. This project will start to expose how the brain’s immune response may cause symptoms in dementia and reveal new targets in the hunt for treatments. Research like this is hugely important to help translate genetic findings into tangible biological processes that could be targeted for treatments.
Dr Barry McColl
University of Edinburgh
1 October 2015 - 30 September 2018
Full project name
Contribution of TREM2 and neuroinflammation to neurodegeneration and cognitive dysfunction in response to chronic cerebral hypoperfusion
TREM2: Where are we now?
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