Study Links Brain Epigenetic Changes and Tau Accumulation to Alzheimer's Pathology

Scientists know that age is the greatest risk factor for Alzheimer's disease, but aging alone doesn't explain why some people develop the condition while others do not. Genetics, lifestyle factors and environmental influences also appear to play a role. Researchers are working to understand how these factors interact in the brain, explains Nilüfer Ertekin-Taner, M.D., Ph.D., a neurologist and neuroscience chair at Mayo Clinic in Florida.

Alzheimer's disease is the most common cause of dementia. It affects memory, thinking, behavior and the ability to carry out everyday activities.

For many years, Alzheimer's research has focused on two proteins found in the brain: amyloid and tau. The buildup of these proteins is one of the best-known features of the disease. While these proteins remain important, researchers now recognize that Alzheimer's is a complex disease involving many biological processes beyond amyloid and tau." 

Nilüfer Ertekin-Taner, M.D., Ph.D., Neurologist and Neuroscience Chair, Mayo Clinic

A recent Mayo Clinic study explored another piece of the puzzle: changes in how the brain turns genes on and off.

Genes are sections of DNA that provide instructions for how cells work. Cells can control which genes are active and which remain inactive, allowing them to carry out different functions without changing the underlying DNA sequence. Scientists call this process epigenetics. These chemical changes can influence how cells behave and respond to aging, disease and environmental factors. 

In the study, researchers examined brain tissue from hundreds of people with Alzheimer's disease and looked for patterns in these gene-regulating changes. They identified several changes strongly linked to the tau protein. 

The research also highlighted the possible importance of oligodendrocytes - brain cells that support nerve cells by producing myelin, a protective layer that helps signals move efficiently. When myelin is damaged, communication in the brain may be disrupted.

"The findings suggest that Alzheimer's disease may involve not only damage to nerve cells but also changes in the systems that support how those cells communicate with one another," explains Dr. Ertekin-Taner, the study's senior author. "This growing understanding is encouraging researchers to look beyond traditional explanations of the disease."

So, what does this mean for patients today?

These findings are not expected to change how Alzheimer's disease is diagnosed or treated right now, Dr. Ertekin-Taner says: Scientists must confirm the findings, better understand how these changes affect the brain and determine whether the discoveries can lead to safe and effective treatments. 

"One reason researchers are excited about epigenetics is that, unlike inherited DNA changes, some gene-control changes may be reversible," she adds. "While much more research is needed, the findings so far suggest that future therapies could target these biological processes." 

Studies like this also help identify new areas for investigation and may reveal why Alzheimer's disease affects people differently, Dr. Ertekin-Taner says. As researchers learn more, they move closer to developing more personalized approaches to prevention and treatment. 

The Mayo Clinic team that did research on the DNA changes associated with the disease also created a free online tool that allows researchers worldwide to explore the study's data. Called the Multiomic Atlas of AD Brain Endophenotypes, the searchable resource lets scientists look up specific genes and view results in interactive tables and graphs.

By making these findings widely available, researchers hope to accelerate discoveries and support the development of improved treatments for Alzheimer's disease and other neurological conditions.