BRACE has funded many genetic research projects over the years, which have resulted in over 50 genetic research papers.

Genetic research is important in Alzheimer’s disease in several ways. Through genetic research, genes which make people more susceptible to dementia can be identified. This improves understanding of the biological processes in Alzheimer’s disease, as well as enabling the development of drug treatments which may act on these processes. It can also reveal who might be at risk of Alzheimer’s.

Many studies involve Genome-wide association studies (GWAS) methods. This method involves screening the entire genome of groups of participants and examining the variation between healthy people and people with Alzheimer’s. Genes vary due to small mutations, called single nucleotide polymorphisms (SNPs). BRACE has funded multiple GWAS studies which aim to search for this variation, and over 20 variants have been found. By finding which variants are statistically more likely to be found in people with Alzheimer’s disease, we are able to further understand which genes and biological pathways are involved. This is possible by researching how the variation causes changes in the brain and how it differs in healthy controls. BRACE funded work by Dr. Shelley Allen and Dr. David Dawbarn in 1997 discovered that a genetic variation in the gene Apoe4 lowers cholinergic function. They later showed that this reduced cholinergic activity correlated with disruption of the pathways involved in processing the main protein thought to be involved in Alzheimer’s disease: Amyloid-β. This was therefore an important discovery in terms of establishing which biological processes are involved in Alzheimer’s and how the disease occurs.

As well as GWAS studies, BRACE has also funded research into looking at how genes may work differently in Alzheimer’s disease. For example, the way that genes make proteins can change as a result of chemical modifications such as methylation (when methyl groups are added to genes). Methylation reduces the amount of protein that genes make. Methylation of specific genes may play a role in AD: BRACE funded work by Dr Katie Lunnon and Dr Adam Smith has shown that the gene TREM2 is significantly more methylated in Alzheimer’s disease brains compared to healthy brains. TREM2 plays a role in clearing dying neurons from the brain and regulating inflammation so methylation of this gene may disrupt these processes.

This is useful research as epigenetic changes such as methylation can be reversible, so this research may lead to the discovery of potential drug targets. Methylation can be affected by many environmental factors, so further work is also needed to establish how lifestyle factors may be involved.

 By Rachel Milligan, University of Bristol

From the report by Travis Bacon, also University of Bristol, into BRACE’s impact 1987-2017

Image by NICHD