Investigating whether changes to chemical DNA tags contribute to Alzheimer's disease

Lead Investigator: Dr Katie Lunnon

Institute: University of Exeter

Grant Type: Project Grant

Amount: £201,732

Duration: 30 months

Scientific Title: The contribution of epigenetic phenomena to Alzheimer's disease: an integrated genetic-epigenetic analysis

Why did we fund this project?

Comments from the Research Network:

'Excellent, complex and potentially very useful and informative analysis of pre-existing data'

'A very exciting field of research. I look forward to following the progress of the project'

'Could help identify causes and patterns of Alzheimer's disease so could be important'

What do we already know?

Alzheimer's disease develops due to the loss of brain cells, caused by the build-up of sticky proteins. Curiously, this brain cell loss only occurs in some areas of the brainwith those involved in learning and memory particularly affected. Other regions are relatively resistant to damage. 

The genetics behind the development of the most common form of Alzheimer's are complex, and there is no known single genetic cause. Although a number of large-scale studies have searched for new genes that may make an individual more susceptible to disease, most of the identified genetic changes only have a very modest effect on influencing the risk of disease development. 

Small changes in the DNA that makes up a gene have been shown to influence the risk of developing certain conditions. It is also known that gene function can be altered by an extra level of information called the 'epigenome'. Epigenetic processes are chemical tags that are added to the DNA associated with a particular gene, and can influence a gene's function without altering its makeup. Epigenetic changes can be influenced by external factors such as the environment. As it has been hard to find differences within the genes themselves that can influence Alzheimer's disease development, some researchers are investigating whether epigenetic changes also play a role. 

The researchers on this project, Dr Katie Lunnon and Professor Jonathan Mill, were part of a team that has previously discovered a link between a particular epigenetic change known as methylation and Alzheimer's disease. This research was particularly groundbreaking as some of their results were verified independently by another scientific group in the US. 

What does this project involve?

This project is a collaboration between several experts based in the UK and the US. The researchers will use large sets of clinical, genetic and molecular data to address several questions surrounding the onset of Alzheimer's disease. These questions include finding out why certain brain regions are more susceptible to the disease and why some people are more likely to be affected than others. They also aim to investigate whether it is possible to develop a blood test that will aid in diagnosis and finally they will try to uncover new mechanisms that could be used as targets for treatments.

The researchers intend to use huge datasets to discover whether there are any epigenetic changes that are associated with risk of developing Alzheimer's disease, particularly focusing on methylation. They will also determine whether epigenetic changes combined with changes to the gene itself can contribute towards Alzheimer's disease. They will also investigate whether any epigenetic changes that are associated with disease development can be identified using a blood test.

How will this benefit people with dementia?

The genetics behind Alzheimer's disease have proven very difficult to clarify. This fresh approach to investigating genes via epigenetics may help to shed new light the role that DNA has during Alzheimer's development. If understanding in the field is increased, it will help with finding new areas to target with potential therapies. 

Diagnosis of Alzheimer's disease can sometimes be difficult, as it is not always easy to distinguish between Alzheimer's and other causes of dementia. If this study can use epigenetics to develop a blood test that helps with diagnosis then this would allow people affected to access the support, information and treatments that they need.