The largest study of its type has unveiled new insights into how genes are controlled in dementia, such as discovering 84 new genes related to the disease.
Led by the University of Exeter, the worldwide collaboration combined and analysed data from over 1,400 individuals across six distinct research, in a meta-analysis printed in Nature Communications. These studies had used brain samples from people who had died with Alzheimer’s disease. The project, financed by Alzheimer’s Society and supported by the Medical Research Council and the National Institutes for Health, seemed at an epigenetic mark known as DNA methylation at almost half a million sites in the genome. Epigenetic processes control the degree to which genes are switched off and on, meaning that they act differently as needed across the different cell-types and cells that make up a human body. Significantly, unlike our genes, epigenetic processes can be affected by environmental factors, making them possibly reversible and a potential path to new therapies.
The study looked at epigenetic patterns throughout the genome, in several of different regions of the mind. The team then related the quantity of DNA methylation to the sum of neurofibrillary tangles within the mind, which is a significant hallmark of the seriousness of Alzheimer’s disease.
The group looked in different regions of the mind, which are affected in Alzheimer’s disease before searching for frequent changes across these cortical areas. They identified 220 sites in the genome, such as 84 new genes, which demonstrated different levels of DNA methylation from the cortex in individuals with more severe Alzheimer’s disease, which weren’t seen in a different region of the brain called the cerebellum.
The team went on to demonstrate that a subset of 110 of these sites could differentiate in two independent datasets whether a brain sample had high or low levels of disorder, with more than 70 percent accuracy. This suggests that epigenetic changes in the brain in Alzheimer’s disease are very consistent. The findings were subsequently confirmed in an independent group of brain samples from the Brains for Dementia Research cohort funded by the Alzheimer’s Society and Alzheimer’s Research UK.
Professor Katie Lunnon, at the University of Exeter, who led the study, said:”Our study is the largest of its kind, giving important insigh