Understanding how tiny changes in several genes could contribute towards risk of Alzheimer’s disease

Read about a research project we funded into the regulatory genomic consequences of polygenic risk burden for Alzheimer's disease.

Lead Investigator: Professor Jonathan Mill 
Institution: University of Exeter
Grant type: PhD
Duration: 36 months
Amount:  £85,000

Why did we fund this project?

Comments from members of our Research Network:

'An interesting project which may lead to a better understanding of Alzheimer's disease'

'A good team is supporting this project, which must continue to have funding'

'We seem to understand so little around the genetic risk of dementia - this study could help us to know rather more.'

What do we already know?

The causes of Alzheimer's disease are thought to be a complex mix of genetics, lifestyle and environmental factors. Variations in the gene ApoE are known to increase risk of Alzheimer's disease, but this gene alone is not enough to cause Alzheimer's. Researchers have made a lot of progress in identifying regions or areas of our DNA other than ApoE that are linked to the development of Alzheimer's. However, pinpointing the exact genetic links to the condition has proven difficult. 

Recent advances in technology now mean that it is possible to study large amounts of DNA in a relatively short space of time. Using this technology, researchers have uncovered tiny variations in hundreds of genes that could be linked to the development of Alzheimer's disease. It is thought that a combination of many of these variations could be a major contributing factor to a person's risk of developing the condition. This combination of genetic variations is known as a 'genetic risk score'. Someone with many variations linked to Alzheimer's disease will have a 'high' genetic risk score. 

What does this project involve?

The researchers on this project have previously linked chemical tags added to DNA (known as 'epigenetic' tags) to a person's risk of developing Alzheimer's disease. These tags control the activity of the genes, turning them 'on' or 'off'. 

The student on this project will analyse samples of DNA from over 26,000 people. They will use this data to understand how a high genetic risk score affects this pattern of chemical tags, and vice versa. They will also understand how these tags are related to genetic changes associated with Alzheimer's disease. They can use this information to narrow down genetic regions that are likely to contribute to Alzheimer's disease risk. 

How will this benefit people with dementia?

Understanding the genetic risks of Alzheimer's disease remains a high priority for researchers, as these genetic factors could be suitable targets for future treatments. This knowledge will also help researchers to understand more about the underlying molecular processes that cause Alzheimer's disease. 

The findings from this research will help to narrow down the search for genetic causes of Alzheimer's disease. These findings could be used to design and develop specific drugs that could stop the disease in its tracks. 

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