Epigenetic Blood Marker Studies Can Help Evaluate Dementia Risk

Scientists report that epigenetic markers in the blood could be useful for understanding dementia risk. Two linked papers from the University of Exeter and Maastricht University show the potential for DNA methylation in understanding how genetics and lifestyle factors influence dementia risk.

Assessing DNA methylation can help researchers understand the extent to which these different factors influence the risk of dementia and the mechanisms by which they bring about disease.

The studies appear in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association. Teams 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 clinical information on participants, who all provided samples of spinal fluid used for 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 instead use blood samples. Analyzing blood epigenetic signatures that are associated with Alzheimer’s disease biomarkers would be cheaper and easier to collect in practice.

In the first paper, “Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer’s disease in the EMIF-AD study,” investigators led by Katie Lunnon, PhD, at the University of Exeter Medical School, showed that DNA methylation signatures in blood can mirror some protein biomarker levels in spinal fluid samples, which are used for assessing dementia. The team explored these signatures in conjunction with 15 different spinal fluid biomarkers that are used for diagnosing dementia and showed changes in the methylation status of key genes for a number of these biomarkers.

“We know that a number of genetic and lifestyle factors can increase the risk of developing Alzheimer’s disease and other dementias,” said Lunnon. “Epigenetics is a particularly exciting research field because it can mediate the interaction between our genetic makeup, which is fixed at conception, and environmental risks, which we can potentially modify.”

In the second paper, “Blood-based multivariate methylation risk score for cognitive impairment and dementia,” Ehsan Pishva, MD, PhD, and colleagues at Maastricht University generated epigenetic risk scores using blood DNA methylation signatures as a proxy for 14 known dementia risk factors. Some of these were modifiable lifestyle risks including physical activity and diet and some were non-modifiable, such as age and having heart disease.

The researchers 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 to better lifestyle management, and to accessing potential new treatments. The paper highlights how genetic, lifestyle, and environmental factors contribute to the development and progression of dementia through epigenetic mechanisms.

“Our epigenetic risk score can improve the prediction of risk of cognitive impairment in different populations, marking a significant advancement in dementia research,” noted Pishva. “The study, which involved advanced analysis of large epigenetic datasets from multiple independent dementia cohorts, found that the epigenetic risk score was a predictor of future cognitive decline in Alzheimer’s disease and Parkinson’s disease cohorts.

“Our findings highlight the potential of using blood-derived epigenetic measurements as a noninvasive approach to assess dementia risk, paving the way for future studies to explore more personalized and preventive healthcare strategies in tackling cognitive impairment.”