New research suggests that epigenetic markers in the blood could be useful for understanding dementia risk. Two linked papers from the University of Exeter and Maastricht University have jointly advanced research to demonstrate the potential of DNA methylation, an epigenetic marker, for understanding the influence of genetics and lifestyle factors on dementia risk.
DNA Methylation Signatures in the Blood Are Very Informative
DNA methylation is a chemical marker on DNA that can switch genes on and off. Genetic and lifestyle factors can alter the amount of DNA methylation marker on genes, and some of these factors are already known to increase the risk of developing dementia. Assessing DNA methylation can help scientists understand the extent to which these different factors influence dementia risk and the mechanisms by which they trigger the disease.
In the largest study of its kind, published in Alzheimer’s and Dementia: the Journal of the Alzheimer’s Association, researchers examined DNA methylation at 800,000 sites in the genome in blood samples taken from 900 individuals as part of the EMIF-AD MBD (European Medical Information Framework for Alzheimer’s disease Multimodal Biomarker Discovery) study. The study contains extensive clinical information on the participants, all of whom provided samples of spinal fluid, which is used for the diagnosis and monitoring of Alzheimer’s disease as it is in direct contact with the brain. However, as collecting spinal fluid is an invasive procedure, the team investigated whether they could use blood samples instead by analyzing epigenetic signatures in the blood that are associated with biomarkers of Alzheimer’s disease, as this would be cheaper and easier to collect in practice.
In the first of the two papers, led by Professor Katie Lunnon of the University of Exeter Medical School, the team showed that DNA methylation signatures in blood can reflect some protein biomarkers in spinal fluid samples that are used to assess dementia. The team examined these signatures in conjunction with 15 different biomarkers in spinal fluid used to diagnose dementia and showed changes in the methylation status of key genes for a number of these biomarkers.
14 Known Dementia Risk Factors
In a second linked article in the same journal, the team, led by Dr. Ehsan Pishva of Maastricht University in the Netherlands, created epigenetic risk scores using DNA methylation signatures in blood as proxies for 14 known dementia risk factors. Some of these were modifiable lifestyle risks such as physical activity and diet, while others were not modifiable, such as age and heart disease.
They showed that their epigenetic risk scores can improve the prediction of risk of cognitive decline and onset of dementia, even at early stages. Early detection is crucial for a better lifestyle and access to potential new treatments. The study highlights how genetic, lifestyle and environmental factors contribute to the development and progression of dementia via epigenetic mechanisms.
Professor Katie Lunnon from the University of Exeter Medical School is the lead author of one of the studies and leads the Dementia Genomics team, which has already published a number of groundbreaking papers exploring epigenetics in the brain and blood in various dementias. According to Lunnon, it is known that a number of genetic and lifestyle factors can increase the risk of developing Alzheimer’s disease and other dementias. Epigenetics is a particularly exciting area of research because it can mediate the interaction between our genetic makeup, which is determined at conception, and environmental risks that we may be able to modify.
Using Epigenetic Measurements From Blood as a Non-Invasive Approach to Assess Dementia Risk
According to Dr. Ehsan Pishva of Maastricht University, who authored the other paper and leads the Systems Biology of Dementia team, our epigenetic risk score can improve the prediction of risk of cognitive impairment in different populations, and thus represents a significant advance in dementia research. The study, which involved an advanced analysis of large epigenetic datasets from several independent dementia cohorts, found that the epigenetic risk score is a predictor of future cognitive decline in Alzheimer’s and Parkinson’s cohorts. According to the researchers, these results highlight the potential of using epigenetic measurements from blood as a non-invasive approach to assess dementia risk and pave the way for future studies exploring more personalized and preventive health strategies to combat cognitive impairment.