Researchers examined DNA methylation across 800,000 locations in the genome using blood samples from 900 participants. The study incorporates detailed clinical data from these individuals, all of whom also provided spinal fluid samples that are utilized for diagnosing and tracking Alzheimer’s disease due to their direct connection to the brain. However, since obtaining spinal fluid is an invasive procedure, the researchers aimed to determine if they could utilize blood samples instead. They analyzed blood epigenetic signatures linked to Alzheimer’s disease biomarkers as a more cost-effective and less invasive alternative.
Recent findings indicate that epigenetic markers in blood may play a key role in assessing dementia risk.
Two connected studies from the University of Exeter and Maastricht University have advanced research demonstrating the promise of DNA methylation, an epigenetic marker, in understanding how both genetic and lifestyle choices contribute to dementia risk.
DNA methylation involves a chemical modification added to DNA that can regulate gene activity. Changes in genetic and lifestyle factors can affect the levels of DNA methylation, and some of these aspects are already known to elevate the risk of developing dementia. By evaluating DNA methylation, scientists can gain insights into how various influences impact dementia risk and the underlying mechanisms of the disease.
In what is the largest study of its kind published in Alzheimer’s and Dementia: the Journal of the Alzheimer’s Association, researchers checked DNA methylation across 800,000 genomic sites in blood samples from 900 participants in the European Medical Information Framework for Alzheimer’s disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. The research includes comprehensive clinical data from the participants, all of whom provided spinal fluid samples used in Alzheimer’s disease diagnosis and monitoring. Given the invasive nature of fluid collection, the researchers sought to use blood samples instead by examining blood epigenetic markers linked to Alzheimer’s disease biomarkers, which would offer a more practical and economical collection method.
The first paper, led by Professor Katie Lunnon from the University of Exeter Medical School, demonstrated that DNA methylation patterns in blood can reflect the levels of certain protein biomarkers found in spinal fluid that are used for diagnosing dementia. The research assessed these patterns alongside 15 different spinal fluid biomarkers for dementia diagnosis, revealing alterations in methylation levels for several of these key biomarkers.
The second paper, directed by Dr. Ehsan Pishva at Maastricht University in the Netherlands, developed epigenetic risk scores employing blood DNA methylation patterns as indicators for 14 known dementia risk factors. Some of these factors, like physical activity and diet, are modifiable lifestyle risks, while others, such as age and preexisting heart conditions, are non-modifiable.
The findings indicated that the epigenetic risk scores can enhance predictions of cognitive decline and the onset of dementia, even in its early stages. Detecting these risk factors early is essential for better lifestyle management and accessing new treatment options. The study showcases how genetic, lifestyle, and environmental influences contribute to dementia development and progression via epigenetic processes.
Professor Katie Lunnon, a lead author of one of the studies and head of the Dementia Genomics Team, has previously published innovative research delving into epigenetics in both the brain and blood concerning various forms of dementia. She remarked, “We know that many genetic and lifestyle factors can elevate the risk of Alzheimer’s disease and other forms of dementia. The field of epigenetics is particularly fascinating as it can bridge the gap between our inherited genetic traits, which remain static from conception, and the environmental risks that we have the ability to change.”
Dr. Ehsan Pishva, leading the other paper at Maastricht University and the Dementia Systems Biology team, noted, “Our epigenetic risk score can enhance the prediction of cognitive impairments across various populations, marking a significant breakthrough in dementia research. This study, which involved detailed analyses of extensive epigenetic datasets from multiple independent dementia cohorts, showed that the epigenetic risk score could predict future cognitive decline in groups with Alzheimer’s disease and Parkinson’s disease.”
“These findings demonstrate the potential of blood-derived epigenetic metrics as a non-invasive method for evaluating dementia risk, laying the groundwork for future research focused on personalized and preventive healthcare strategies to address cognitive decline.”
The EMIF-AD MBD initiative was supported by the Innovative Medicines Initiative Joint Undertaking, with additional funding for the work described in these publications provided by the Alzheimer’s Society, Medical Research Council, National Institute on Aging of the National Institutes of Health, and ZonMw Memorabel/Alzheimer Nederland. Further backing was also offered by the NIHR Exeter Biomedical Research Centre.
