Study of rare genetic variants in Alzheimer's disease

Lead researcher: Dr Rebecca Sims
Institution: Cardiff University
Grant type: Fellowship
Duration: 3 years
Amount funded: £211,281

Scientific title: Powerful study of rare variants in Alzheimer's disease

Why did we fund this project? Comments from members of our Research Network:

'This is indeed a powerful study. I am impressed by its content and also by the breadth of ongoing work to which it can potentially contribute.'

'This is a highly ambitious project which could have far reaching beneficial findings.'

'This is clearly pioneering work and it is possible applications would be vital in assisting early identification of the suspect genes.'

What do we already know?

Alzheimer's disease is the most common form of dementia, yet we still do not fully understand what causes it, including which genes may play a role.

There has been a lot of work understanding and investigating certain genes that increase the risk of developing Alzheimer's disease; there are three known genetic mutations that exist in a very small number of families that results in the development of early-onset Alzheimer's disease. There has also been work investigating other genes that increase the risk of developing the disease, including ApoE4, for which there is the most evidence. Although having these genes may increase your risk, they do not mean that you will definitely develop the disease.

In order to understand the underlying causes of Alzheimer's disease and the changes that occur, it is important to find copies of certain genes that may increase the risk of developing it; by finding these genes, we can work to understand the role that they play, and be able to more accurately target the changes in the brain that these genes may cause.

What does this project involve?

This fellowship will aim to identify new genes that contribute to the development of Alzheimer's disease and develop new techniques to identify genes that affect disease development.

To do this, the researcher will decode the genetics of a large number of people, some with Alzheimer's disease, some who are elderly but don't have Alzheimer's, and others who will act as controls by representing the general population. This will allow the researchers to see what genes are found more often in people with Alzheimer's disease than we would expect to see in the population (for example, if a particular gene is seen in 10% of the general population, but 40% of people with Alzheimer's disease, this gene could be related to the disease).

Any genes that are identified will be further investigated to see if these genes do play a role in the development of Alzheimer's disease and if there are specific areas within the gene that can be identified as potential causes of this.

This will be the first time that a general search for these genes will be performed for Alzheimer's disease.

How will this benefit people with dementia?

Genes vary across the population, and discovering more of these variations that have implications for the development of Alzheimer's disease will help scientists to further understand the causes of the disease.

Genes are responsible for making proteins (the 'building blocks' of the body), which in turn affect how well particular processes work. Understanding how different forms of a particular gene may result in slight differences in the proteins made could lead scientists closer to understanding the role that these particular processes play in the development of Alzheimer's disease.

By further understanding what changes lead to Alzheimer's disease, researchers can start to target these and stop disease progression, via drugs or other treatments.