Alzheimer’s Research UK recently awarded a £96,000 grant to Prof Kevin Morgan at the University of Nottingham to maintain and expand his large collection of DNA samples. This is to ensure he can continue his important research into the genetics of Alzheimer’s disease. These huge DNA banks are an essential tool for Alzheimer’s research; the bank run by Prof Morgan has already helped in the identification of 21 Alzheimer’s risk genes, with more discoveries to come. These discoveries are vital to help researchers understand the biology behind Alzheimer’s. They are also the first step towards finding areas which may be useful targets for the development of new treatments.
We know that Alzheimer’s is caused by a mixture of genetic and environmental factors alongside the biggest risk factor of age. This video explains that, in the majority of cases, Alzheimer’s is not caused by a single faulty gene. Instead, it appears that small changes in several different genes contribute to disease development. These small genetic changes affect a variety of molecular functions.
Investigating genetic changes
The best way to understand the genetic changes in Alzheimer’s is through large-scale studies. These studies are known as Genome-Wide Association Studies (GWAS) and at best, involve hundreds or even thousands of DNA samples. The samples are donated by people with Alzheimer’s and those of a similar age and background but who don’t have the disease.
Researchers can then analyse the genetic makeup of the volunteers in extreme detail. They use statistical analysis to reveal common genetic changes which appear more often in people who have the disease. This flags up genes (called ‘risk’ genes) that may be contributing to the development of Alzheimer’s.
The bigger the better
As with all statistical analysis, the more samples the better. Investigating Alzheimer’s genetics is especially complicated because, due to the multiple factors thought to contribute to disease development, having a risk gene does not necessarily mean you will get the disease. Changes in these risk genes can also be very subtle and therefore hard to detect.
For example, imagine you were investigating a gene (GENE) and you know that two different versions of this gene occur naturally in the population – GENE1 and GENE2.
You suspect that having GENE2 may be a risk factor for Alzheimer’s disease.
However, if you did a larger study with many more samples, you may start to see differences. If you have a large enough set of samples, it may become clear that GENE2 does associate with the disease. Larger scale studies are especially useful for finding genetic changes which are rare or only contribute to Alzheimer’s in certain groups of people.
Large DNA banks can also help researchers to find combinations of genes which might work together to increase our risk of Alzheimer’s. As Alzheimer’s is known to be caused by many small genetic changes, someone who has three risk genes may be more likely to develop Alzheimer’s than someone who has a change in a single gene. Statistical analysis can link these risk genes together and larger samples give researchers a more accurate result.
Genetics and environment
Another way DNA banks are useful is to help tease apart genetic and environmental risk factors for Alzheimer’s. If all of the DNA you are studying is from volunteers living in the same area, such as London, then you cannot rule out that some aspect of living in London is contributing to the disease. However, if your samples come from all over the world, these environmental effects get diluted out making the genetic effects clearer to measure.
Gathering, maintenance and organisation of sample sizes which are large enough to do comprehensive analysis requires a monumental amount of management. GWAS studies, along with other large-scale techniques, have already contributed greatly to our understanding of the genetics behind Alzheimer’s, but there is more left to be discovered. As well as helping us to understand why the disease develops, finding these genetic contributions to Alzheimer’s will aid researchers in finding new areas which can be used as targets for treatment.
This is why Alzheimer’s Research UK encourages and funds the maintenance of large DNA banks such as the one managed by Prof Morgan and his team. The more data available, and the more varied it is, the better chance we have of understanding the genetics of Alzheimer’s and translating that understanding into benefits for people with dementia.