Understanding whether chemical DNA tags affect the immune system in the development of Alzheimer’s disease

Research project: Molecular characterisation of the role of systemic infections in Alzheimer's disease brain 

Lead Investigator: Dr Katie Lunnon
Institution: University of Exeter
Grant type: Project grant
Duration: 36 months
Amount: £361,535

Why did we fund this project?

Comments from members of our Research Network:

“The identification of new disease pathways and genes that are involved in the disease process [which] could be the target of drug development programmes is a vital outcome from this work.”

“This looks like a very promising area of research which could ultimately lead to effective treatment of Alzheimer's disease. The research team would bring excellent skills and experience to the project.”

“This proposal appears to mark an unusually sophisticated approach to the study of the role of genes in the development of dementia.”

What do we already know?

The immune system is thought to play a key role in the development of Alzheimer’s disease. Specialist immune cells in the brain called microglia are particularly thought to contribute towards the disease process. One theory is that the microglia overreact to infections, producing a large number of chemicals that fight the infection but that also cause the death of brain cells.

There is also evidence that contracting an infection, especially in older people, may contribute towards dementia development or speed up decline in memory and thinking abilities.

Research has also uncovered genetic links for Alzheimer’s disease but it is clear that this is not the whole story. Dr Lunnon and her team specialise in investigating chemical tags that are added to our DNA that can change the way our genes behave. These tags are called ‘epigenetic’ and can be influenced by factors such as the environment. As it has been hard to pinpoint specific genetic causes of Alzheimer’s disease, the team believes that epigenetics may also play a role in the risk of developing the condition. 

Bringing these two concepts together, Dr Lunnon believes that inflammation in the body due to an infection can cause epigenetic changes to microglia. This causes the microglia to behave differently and potentially contribute towards disease progression. 

What does this project involve?

The researchers will use brain tissue donated via the Brains for Dementia Research programme to understand the epigenetic changes that occurred in people who had an infection at the time that they passed away. They will compare people with Alzheimer’s to those who didn’t have the disease.

They will also investigate whether there are differences between people who had an infection and those who didn’t.

The team will then look closer at the microglia taken from some of the donors to further measure and understand the epigenetic changes that they have identified. 

Once they have identified any epigenetic changes associated with microglia in their samples, the team hope to apply for further funding to test these changes on human cells grown in the lab. They can then use these to understand whether there are any treatments that can reverse the effect on microglia. 

How will this benefit people with dementia?

The exact causes of dementia remain elusive and although it is known that genetics and the immune system both have a role, it is unclear exactly what these roles are. This innovative approach will use cutting-edge techniques to understand more about these important contributors to the development of Alzheimer’s disease. Once these mechanisms are better understood, that would clear the way to find ways to target them with potential treatments.