Epigenetics study reveals how genes are regulated in dementia

A study has identified 84 new genes linked to Alzheimer's disease by combining and analysing data from over 1400 people.

An international collaboration, led by the University of Exeter, studied DNA methylation across nearly half a million sites in the genome in order to identify epigenetic changes linked with the disease. Epigenetic processes influence how a cell behaves by regulating our genes, however, unlike our genes which are inherited, epigenetic changes occur throughout our lives and can be caused by environmental factors.

'Our study is the largest of its kind, giving important insights into genomic areas that could one day provide the key to new treatments. The next step for this work is to explore whether these epigenetic changes lead to measurable changes in the levels of genes and proteins being expressed. This will then allow us to explore whether we could repurpose existing drugs that are known to alter the expression levels of these genes and proteins, to effectively treat dementia' said lead author Professor Katie Lunnon of the University of Exeter.

This meta-analysis, published in Nature Communications, combined data from six studies and compared the amount of DNA methylation to the number of neurofibrillary tangles, a key hallmark of Alzheimer's disease which is associated with disease progression. The team identified DNA methylation at 220 genomic sites (including 84 previously unidentified genes) in samples from the cortex, the area of the brain predominantly effected by Alzheimer's disease. A subset of 110 sites were then able to predict high or low levels of disease progression with 70 percent accuracy in two independent datasets. This suggests that epigenetic changes across the brains of people with Alzheimer's disease are very consistent.

Dr Richard Oakley of the Alzheimer's Society, which part-funded the research, commented that 'Epigenetics is a flourishing area of dementia research. It's now important to delve into the specific impact of these epigenetic changes and the associated genes on the changes in the brains of people with Alzheimer's disease. This work is in early stages but breakthroughs in research begins with work like this, and it brings us a step closer to developing new treatments for Alzheimer's disease.'

This work was also supported by the UK's Medical Research Council and the US's National Institutes of Health and Alzheimer's Association, and included researchers from the USA (Columbia University and Mount Sinai School of Medicine in New York, Rush University Centre in Chicago, Illinois, and Arizona State University in Tempe, Arizona), the Netherlands (Maastricht University), and Germany (University of Saardland).