A large-scale study led by the University of Exeter has revealed new insights into the way genes are regulated in dementia, discovering 84 new genes linked to the disease. Published in the journal Nature Communications, the research analyzed data collected from more than 1,400 people as part of six previous studies, which made use of brain samples taken from deceased Alzheimer’s patients.
The Exeter study focused on DNA methylation, an epigenetic mark (a change to DNA), at around 500,000 sites in the genome. Epigenetic processes determine how much genes are switched on and off, and unlike genes they can be affected by environmental factors. This means it is possible to reverse them, which could help produce new treatments for certain diseases.
The researchers linked the amount of DNA methylation to the number of neurofibrillary tangles in the brain – these are clumps of protein associated with Alzheimer’s, which can be studied to determine the severity of the disease in an individual patient. They first looked at different parts of the brain known to be affected by Alzheimer’s before seeking out common changes across the various regions. As a result, they identified 220 sites in the genome (the complete set of genetic information in an organism that is required for it to function) and 84 new genes that had different levels of DNA methylation in the cortex of people with severe Alzheimer’s disease.
They then discovered that 110 of these sites were able to determine whether a brain sample had high or low levels of disease with an accuracy of more than 70 percent, which suggests that Alzheimer’s disease involves highly consistent epigenetic changes (changes to the physical structure of DNA) within the brain.
The research team now wants to focus its efforts on working out whether these epigenetic changes cause measurable changes to the number of genes and proteins that are expressed (gene expression is the process where the information contained in a gene is used to assemble a protein molecule). They believe that their findings could ultimately lead them to discover ways of repurposing existing drugs to effectively treat dementia. The study has also been hailed as marking progress towards understanding the role genes play in Alzheimer’s disease.