A team led by researchers at the University of Exeter Medical School and King's College London has uncovered some of the strongest evidence yet that epigenetic changes in the brain play a role in Alzheimer's disease. Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence and are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies. Globally, more than 26 million people are currently affected by Alzheimer's disease. As this number grows in line with an increasingly aging population, the need to identify new disease mechanisms is more important than ever. Post-mortem examinations have revealed much about how Alzheimer's damages the brain, with some regions, such as the entorhinal cortex, being particularly susceptible, while others, such as the cerebellum, remain virtually unscathed. However, little is yet known about how and why the disease develops in specific brain regions. The current study found that chemical modifications to DNA within the ANK1 gene are strongly associated with measures of neuropathology in the brain. The study, published in Nature Neuroscience, found that people with more Alzheimer's disease-related neuropathology in their brains had higher levels of DNA modifications within the ANK1 gene. The finding was particularly strong in the entorhinal cortex, and also detected in other cortical regions affected by the disease. In contrast, no significant changes were observed in less affected brain regions or blood.
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