Can the Damage of Alzheimer’s Be Undone?

A new approach to Alzheimer’s disease (AD) research may make it possible to one day reverse memory loss, a hallmark of the disease in its late stages and perhaps its most devastating effect.

A team led by University at Buffalo scientists looking at epigenetics—the mechanisms other than DNA that switch genes on and off—has been able to restore lost cognitive function in mice with AD. Their work paves the way for the future development of drugs that can do the same for human patients.

A key reason for cognitive decline in late-stage Alzheimer’s is a loss of glutamate receptors. Glutamate receptors are found in cells throughout the brain and play an important role in learning and memory.

The researchers discovered that in AD, the loss of glutamate receptors is directly linked to an abnormal epigenetic process called repressive histone modification. They saw an elevation of this abnormal epigenetic process both in the animal models they studied and in post-mortem tissue of AD patients.

Even more exciting: Because this abnormal epigenetic process is controlled by enzymes, it opens the door to targeted drug therapy.

“We have not only identified the epigenetic factors that contribute to the memory loss,” explains Zhen Yan, SUNY Distinguished Professor in the Department of Physiology and Biophysics at UB, and lead author of the study. “We also found ways to temporarily reverse them in an animal model of AD.”

After the AD mice were injected with a targeted enzyme inhibitor, says Yan, they showed “dramatic improvement” in recognition memory, spatial memory and working memory. The improvements lasted one week; future research will focus on developing compounds that penetrate the brain more effectively for longer lasting effects.

Brain disorders such as Alzheimer’s have proven difficult to study and treat because they often involve a number of genes, each with a modest impact. That’s what makes this new finding so promising.

“An epigenetic approach can correct a network of genes, which will collectively restore cells to their normal state,” Yan explains. “If many of the dysregulated genes in AD are normalized by targeting specific epigenetic enzymes, it will be possible to restore cognitive function and behavior.”