Epigenetic changes play role in Alzheimer’s

Researchers say they have amassed some of the strongest evidence yet to show that epigenetic changes have a role to play in Alzheimer’s disease. Researchers from King’s College London and the University of Exeter have found that chemical modifications to DNA within the ankyrin or ANK1 gene is strongly associated with measures of neuropathology in the brain. Researchers performed cross tissue analysis of methylomic variation in Alzheimer’s disease in samples from four independent human post-mortem brain cohorts. They analysed three cortical regions, the cerebellum and blood from several hundred individuals representing the spectrum of disease, from those with evidence of neurodegeneration and dementia, through to patients with very advanced disease. People with more Alzheimer’s disease-related neuropathology in their brains had higher levels of modifications in the ANK1 gene. The finding was particularly strong in the entorhinal cortex – responsible for navigation and memory – and other cortical regions of the brain. “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,” said Dr Jonathan Mill from the Psychiatric Epigenetics Group at King’s. “We don’t yet know why these changes occur – it’s possible that they’re involved in disease onset, but they may also reflect changes induced by the disease itself.” The study, published in Nature Neuroscience, showed differentially methylated regions in ANK1 not only in the entorhinal cortex – the primary site of Alzheimer’s disease manifestation – but in the superior temporal gyrus and prefrontal cortex. No changes were seen in the cerebellum, which appears to be largely protected from Alzheimer’s, or blood. “This innovative research has discovered a potential new mechanism involved in Alzheimer’s by linking the ANK1 gene to the disease,” said Dr Simon Ridley, Head of Research at Alzheimer’s Research, who provided funding for the study. “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.” Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease