Losing control of gene activity in Alzheimer’s disease
New research into the mechanisms controlling gene activity in the brain could hold the key to understanding Alzheimer’s disease.
The research, led by Dr Sarah Marzi from Queen Mary University of London, has uncovered a link between indicators of gene activity and the disease, which could unlock new avenues of research.
Alzheimer’s disease is the leading cause of dementia, which effects 850,000 people in the UK alone. This is set to rise to over 1 million people by 2025.
The research investigated changes to the activity of genes which are not caused by variation in the actual genetic code. Unlike the DNA sequence, these so-called ‘epigenetic’ processes can potentially be altered by environmental factors, providing a possible future avenue to influence their activity.
Giving clues on the genes involved
Dr Marzi, genomics researcher at Queen Mary’s Blizard Institute, said the results of the study could help uncover mechanisms that cause the disease: “Changes influencing the activity of many genes were found to be robustly associated with the pathological hallmarks of Alzheimer’s disease. Interestingly, our results suggest there are common mechanisms for both hereditary and isolated forms of this terrible illness.
“More research is needed to understand whether these changes are a cause or consequence of the disease. Our results may give us clues as to which genes and pathways are involved.”
The researchers studied a type of epigenetic modification called histone acetylation that marks regions of the genome that are active. In cells, DNA is packaged by structures called histones which can be modified to control gene activity. The team quantified levels of histone acetylation across the genome using brain tissue from deceased patients with and without Alzheimer’s disease.
First study of its kind
Both increases and decreases in histone acetylation were found across regions of the genome, identifying genes involved in Alzheimer’s disease. Strikingly, they found differences in regulatory regions controlling the expression of both amyloid and tau, two proteins known to be involved in the pathology of Alzheimer’s disease.
This research is the first genome-wide study to investigate histone acetylation in Alzheimer’s disease, and provides a framework for studying histone modification studies in other diseases affecting the brain.
The study is published in the journal Nature Neuroscience and involved researchers from the University of Exeter and King’s College London, and was funded by the US National Institutes of Health, the European Union and the Medical Research Council.
- Research paper: ‘A histone acetylome-wide association study of Alzheimer’s disease: neuropathology-associated regulatory variation in the human entorhinal cortex’ by Marzi et al. Nature Neuroscience.
For media information, contact:Joel Winston
Faculty Communications Manager (Medicine and Dentistry)