Two independent studies published in the journal Nature Neuroscience have found compelling evidence that epigenetic changes in the brain are involved in Alzheimer’s disease. While it is difficult at this stage to know whether these alterations to DNA are involved in the onset of disease or occur as a result of the disease, the findings are important because they may aid our understanding of the impact of environmental risk factors and lifestyle on Alzheimer’s.
Alzheimer’s is the most common form of dementia, affecting over 26 million people worldwide. The disease involves the progressive degeneration of certain regions of the brain, in particular the cerebral cortex, which results in a variety of symptoms such as memory loss and behavioral changes. While much is known about the brain changes that occur as a result of the disease, little is known about the cause and why it seems to leave some areas of the brain unscathed.
In order to shed light on this poorly understood area, two teams of researchers, one from the US and the other from the UK, investigated post-mortem brain tissue and looked for modifications to the DNA that don’t involve changes to the sequence itself. These changes, known as epigenetic changes, can alter gene expression, for example by switching genes on or off in certain tissues.
“The epigenome is malleable and may harbor traces of life events that influence disease susceptibility, such as smoking, depression and menopause, which may influence susceptibility to Alzheimer’s and other diseases,” lead author of one of the studies Philip De Jager said in a news-release.
For the UK-based study, researchers from the University of Exeter and King’s College London examined the brains of 342 patients that had died of Alzheimer’s. They looked at 3 areas of the brain that suffer significant damage in Alzheimer’s: the prefrontal cortex, the entorhinal cortex and the temporal gyrus. They then compared this with blood samples and tissue from the cerebellum as this is usually unaffected in Alzheimer’s patients.
For the US-based study, Brigham and Women’s Hospital and Rush University Medical Center researchers analyzed prefrontal cortex tissue from 708 people, 60% of whom had Alzheimer’s when they died.
Both studies identified genes that displayed significant changes in methylation levels. DNA methylation switches genes off through the addition of a chemical called a methyl group. The UK team identified 7 genes that showed increased levels of methylation, whereas the US team identified 11. However, 4 of these genes were common to both studies. Furthermore, both teams identified one particular gene that seemed to be significantly affected: ANK1.
The researchers found that ANK1 was hypermethylated in the regions that suffer significant damage in Alzheimer’s patients, but not in the blood or the cerebellum which is largely protected from degeneration. Furthermore, these changes seem to occur early on in the disease, meaning that they could potentially serve as markers to predict patient outcome.
These findings are important because they may help us understand some of the mechanisms involved in the onset of Alzheimer’s, which could eventually be exploited in the development of novel treatments. Indeed, epigenetic changes are potentially reversible, therefore one day it may be possible to target the genes identified in this study to slow disease progression. However, it is currently too early to tell whether these epigenetic changes induce disease or are a result of the disease itself. Further research is therefore warranted to clarify this.
[Via New Scientist and Nature Neuroscience]