Study Reveals Alzheimer’s Patients Have Higher Levels of DNA Modifications in Key Gene

Study Reveals Alzheimer’s Patients Have Higher Levels of DNA Modifications in Key Gene

Alzheimer's DNA ModificationsA research team from the University of Exeter Medical School and King’s College London has uncovered strong evidence of neurological epigenetic changes leading to Alzheimer Disease (AD) development.

There are over 26 million people affected by AD worldwide, a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline.

Despite the increasing population affected by the disease, not much is known regarding its development in specific brain regions, which has led researchers to investigate and pinpoint novel disease mechanisms to fully understand AD and design improved and effective therapies.

Epigenetics refers to functionally relevant changes to the genome that do not change the nucleotide sequence, which means that gene expression can be affected without changing the core DNA sequence. These changes are influenced by the environment and have the capacity to be reverted, becoming potential therapeutic targets.

The study, entitled “Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease” and published in the Nature Neuroscience journal, performed cross-tissue analysis of methylomic variation in AD using samples from four independent human post-mortem brain cohorts.

The team discovered that patients who had a higher level of neuropathology related to Alzheimer’s disease within the brain presented with elevated levels of DNA modifications of the ankyrin 1 (ANK1) gene, especially within the entorhinal cortex region of the brain,a primary site of AD manifestation. Moreover, no substantial changes were observed in the cerebellum or blood obtained pre-mortem from the same individuals.

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“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,” Professor Jonathan Mill of the University of Exeter Medical School and King’s College London and lead author of the study said in a University press release.

To confirm these results, neuropathology-associated ANK1 hypermethylation was further analyzed and confirmed in cortical samples from three independent brain cohorts — the MRC London Brain Bank for Neurodegenerative Disease, the Oxford Thomas Willis Brain Bank, and the Mount Sinai Alzheimer’s Disease and Schizophrenia Brain Bank.

“We know that changes to the DNA code of certain genes are associated with an increased risk of developing Alzheimer’s disease. Investigating how epigenetic changes influence genes in Alzheimer’s is still a relatively new area of study. The importance of understanding this area of research is highlighted by the fact that epigenetic changes have been associated with development of other diseases, including cancer. 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. Alzheimer’s affects millions of people worldwide and we need pioneering research to understand exactly why the disease occurs,” Dr. Simon Ridley, Head of Research at Alzheimer’s Research UK, one of the funding sources for the study, added in the press release.

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