Epigenetic changes linked to Alzheimer's

Researchers have identified a connection between DNA methylation and Alzheimer's disease, gaining a further understanding into the underlying causes of this neurodegenerative condition.

In the first large-scale epigenome-wide association study in this area, researchers at Brigham and Women's Hospital (BWH) and Rush University Medical Center in the USA, found that epigenetic changes in a person's genes may well influence the development of Alzheimer's disease. These epigenetic changes involve 'switching' genes on or off by altering the biochemistry of the DNA.

The research involved analysing post-mortem brain tissue of 708 people who were participants in the Religious Orders Study and Rush Memory and Aging Project. The study's lead researcher, Dr Philip De Jager, expressed the importance of the research:  'Our study approach may help us to better understand the biological impact of environmental risk factors and life experiences on Alzheimer's disease'.

'There are certain advantages to studying the epigenome, or the chemical changes that occur in DNA. The epigenome is malleable and may harbour traces of life events that influence disease susceptibility, such as smoking, depression and menopause, which may influence susceptibility to Alzheimer's and other diseases', he added.

Similarly, a research team at the University of Exeter Medical School and King's College London in the UK has also discovered a link between epigenetic changes in the brain and Alzheimer's disease. This second research project involved analysing post-mortem brain samples from four people.

Professor Jonathan Mill, who participated in both research projects, said: 'This is the strongest evidence yet to suggest that epigenetic changes in the brain occur in Alzheimer's disease, and offers potential hope for understanding the mechanisms involved in the onset of dementia. We don't yet know why these changes occur — it's possible that they are involved in disease onset, but they may also reflect changes induced by the disease itself'.

Both teams screened DNA from human brain tissue samples to look for chemical changes that switch genes off through methylation. In the people who had Alzheimer's disease, several genes were found to have different methylation states in the brain.

Dr Katie Lunnon, from the University of Exeter Medical School, said: 'It's intriguing that we find changes specifically in the regions of the brain involved in Alzheimer's disease. Future studies will focus on isolating different cell-types from the brain to see whether these changes are neuron-specific'.

Results from both studies showed that people with Alzheimer's showed higher levels of DNA modifications in the main brain regions associated with the disease, such as the entorhinal cortex. This finding was particularly strong, in both projects, when the researchers looked at a gene called ANK1, which plays a large role in inflammation and immune activation.

Dr Simon Ridley, head of research at Alzheimer's Research UK welcomed the findings: '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'.

Dr De Jager further discussed how the research may contribute to future advances in treatments for Alzhiemer's disease: 'Our work has helped identify regions of the human genome that are altered over the life-course in a way that is associated with Alzheimer's disease. This may provide clues to treating the disease by using drugs that influence epigenomic function'.