New research suggests that epigenetic markers in the blood may be useful for understanding dementia risk.
Two linked papers from the University of Exeter and the University of Maastricht have jointly advanced research to demonstrate the potential of DNA methylation, an epigenetic marker, to understand how genetics and lifestyle factors influence dementia risk.
DNA methylation is a chemical tag added to DNA that can turn genes on and off. Genetic and lifestyle factors can change the levels of the DNA methylation tag on genes, with some of these factors 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 cause disease.
In the largest study of its kind, published in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Associationresearchers assessed DNA methylation at 800,000 sites in the genome in blood samples collected from 900 people in the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. The study includes extensive clinical information on participants, all of whom provided spinal fluid samples, which have been used for the diagnosis and monitoring of Alzheimer’s disease because it is in direct contact with the brain. However, collecting the fluid is an invasive procedure, so the team investigated whether they could use blood samples instead, analyzing epigenetic marks of blood linked to biomarkers for Alzheimer’s disease, as this would be cheaper and easier in practice. could be collected.
In the first of two papers, led by Professor Katie Lunnon from the University of Exeter Medical School, the team showed that DNA methylation signatures in the blood can reflect certain protein biomarker levels in spinal fluid samples, which are used to assess dementia . The team examined these features in combination with 15 different spinal fluid biomarkers used to diagnose dementia and showed changes in the methylation status of key genes for a number of these biomarkers.
In a second linked paper in the same journal, led by Dr. Ehsan Pishva at Maastricht University in the Netherlands, the team generated epigenetic risk scores using blood DNA methylation signatures as a proxy for 14 known risk factors for dementia. Some of these were modifiable lifestyle risks, including physical activity and diet, and some were non-modifiable risks, such as age and having heart disease.
They showed that their epigenetic risk scores can improve the prediction of the risk of cognitive decline and dementia onset, even at early stages. Early detection is crucial for better lifestyle management and access to potential new treatments. The article highlights how genetic, lifestyle and environmental factors contribute to the development and progression of dementia through epigenetic mechanisms.
Professor Katie Lunnon, at the University of Exeter Medical School, is lead author of one of the studies and leads the Dementia Genomics Team which has previously published a number of groundbreaking papers exploring epigenetics in the brain and blood in different forms of dementia. She said:We know that a number of genetic and lifestyle factors can increase the risk of developing Alzheimer’s disease and other forms of dementia. Epigenetics is a particularly exciting area of research because it can mediate the interaction between our genetic makeup, which is fixed at conception, and environmental risks, which we can potentially modify.
Dr. Ehsan Pishva from Maastricht University, who led the other paper and leads the Dementia Systems Biology team, said: “Our epigenetic risk score can improve the prediction of the risk of cognitive impairment in different populations, representing a significant advance in dementia research. The study, which included a sophisticated analysis of large epigenetic data sets from multiple independent dementia cohorts, found that epigenetic risk score was a predictor of future cognitive decline in the Alzheimer’s and Parkinson’s disease cohorts.
“Our findings highlight the potential of using blood-derived epigenetic measurements as a non-invasive approach to assess dementia risk, paving the way for future studies to explore more personalized and preventative healthcare strategies in addressing cognitive impairment .”
The EMIF-AD MBD project received support from the Innovative Medicines Initiative Joint Undertaking, with the work in these papers further supported by funding from the Alzheimer’s Society, Medical Research Council, National Institute of Aging of the National Institutes of Health and ZonMw. Memorable/Alzheimer’s Netherlands. Further support was also provided by the NIHR Exeter Biomedical Research Centre.
The first article is titled ‘Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer’s disease in the EMIF-AD study. Alzheimer’s and dementia.’
The second article is entitled ‘Blood-based multivariate methylation risk score for cognitive impairment and dementia. Alzheimer’s and dementia.’
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Journal references:
- Smith, R.G. et al. (2024) Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer’s disease in the EMIF-AD study. Alzheimer’s and dementia. doi.org/10.1002/alz.14098.
- Koetsier, J., et al. (2024) Blood-based multivariate methylation risk score for cognitive impairment and dementia. Alzheimer’s and dementia. doi.org/10.1002/alz.14061.