Chemical changes to DNA linked to increased Alzheimer’s disease risk

Researchers at the University of Exeter and King’s College London have discovered that chemical changes to the DNA near the gene ANK1 may play a role in Alzheimer’s disease.

Posted on 19th December 2014

Researchers at the University of Exeter and King’s College London have discovered that chemical changes to the DNA near the gene ANK1 may play a role in Alzheimer’s disease. The findings reveal important clues to the mechanisms underlying the disease that could help improve research into new treatments. The study, helped in part by an Equipment Grant from Alzheimer’s Research UK, is published on xxxx July in the journal Nature Neuroscience.

So-called ‘epigenetic changes’ occur when DNA next to a gene becomes chemically tagged, affecting whether the gene is switched on or off. Researchers believe this to be one way that environment may influence genetics and affect the risk of diseases like Alzheimer’s.

This research concentrated on a particular type of epigenetic change known as DNA methylation. This study pioneered a new technique that investigated the levels of methylation across all of the DNA in areas of the brain called the cortices, which are damaged in Alzheimer’s. The approach, called an Epigenome Wide Association Study (EWAS), compares methylation levels in DNA between people with and without the disease. This is the first time that this kind of study has been used to investigate the mechanisms behind Alzheimer’s disease. As epigenetic changes may be reversible, identifying those involved in Alzheimer’s could provide targets for future treatments.

The researchers studied post-mortem brain tissue from 318 people and found that the DNA next to a gene called ANK1 had very high levels of methylation in the cortices of those who had Alzheimer’s. This high methylation level was not seen in blood, or in an area of the brain called the cerebellum which is not damaged by the disease. The researchers then investigated ANK1 in the cortices using brain tissue from two other independent sources. In each case, excessive methylation of ANK1 was associated with an increased risk of developing Alzheimer’s, suggesting it may play a role in the disease.

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:

“We know that changes to the DNA code of certain genes are associated with an increased risk of developing Alzheimer’s disease. Investigating how epigenetic changes influence genes in Alzheimer’s is still a relatively new area of study. The importance of understanding this area of research is highlighted by the fact that epigenetic changes have been associated with development of other diseases, including cancer.

“This innovative research has discovered a potential new mechanism involved in Alzheimer’s by linking the ANK1 gene to the disease. We will be interested to see further research into the role of ANK1 in Alzheimer’s and whether other epigenetic changes may be involved in the disease.

“Alzheimer’s affects millions of people worldwide and we need pioneering research to understand exactly why the disease occurs. Alzheimer’s Research UK is helping to fund research which will hopefully take us a step closer to understanding and defeating this devastating disease.”

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