Alzheimer's researchers at University of Minnesota reverse memory loss in mice

A top medical researcher at the University of Minnesota has found a new way to reverse memory loss in lab mice, a discovery that could set the stage for a potential human treatment.

Dr. Karen Ashe, a world-renowned expert on Alzheimer's disease, said the research shows that it may be possible for the brain to repair itself, even after the signs of memory loss have appeared.

In a study published this week in the journal Nature Medicine, Ashe and her team found that a natural enzyme called caspase-2 plays a key role in dementia. By lowering the enzyme level, they were able to reverse the memory loss in mice that were genetically altered to mimic the disease.

"Of all the discoveries I've made in my labs, this one has the most potential for becoming an effective drug," said Ashe, who is director of the university's N. Bud Grossman Center for Memory Research and Care.

But she cautioned that it would take years to turn the discovery into a real treatment for patients. "We're trying to develop a pill that would block caspase, but it's a 10-year process even if we're successful," she said.

James A. Hendrix, a scientific director at the Alzheimer's Association, called it an exciting finding, saying, "This could be a new target for drug therapy."

He said the study shed new light on the process that causes Alzheimer's, which has stubbornly defied most efforts at treatment.

But he, too, struck a note of caution. "One has to remember that this [research] is on mice," he said. "We have, unfortunately, successfully treated mice and rats for years, and that hasn't translated to humans. So for a treatment, there's still a long way to go."

This isn't the first time that Ashe has succeeded in reversing memory loss in mice. Her first such study, in 2005, got similar results by turning off a gene that caused the distinctive tangles in the brain associated with Alzheimer's.

The latest study, she said, built on that early work. Ashe and her team discovered that the tangles themselves weren't the cause of memory problems. Instead, they pinned the blame on a protein, called tau, which goes awry early in the process, triggering cell death and memory loss.

When they discovered that an enzyme was causing tau to behave abnormally, they experimented with a drug that cut those enzyme levels in the lab mice.

The result: The brains of mildly impaired mice started to heal themselves. "It restored their memory function back to normal," she said. "What we're doing is repairing the damaged connections between neurons."

If it pans out in people — and that's a big if, she acknowledges — it could help after dementia sets in. "I think you could be mildly to moderately impaired and get back to normal," she said.

Many scientists have been skeptical about the chances of reversing dementia, saying that they're more like to have better luck preventing it than curing the disease.

"The idea of reversal of memory loss, quite frankly, is wishful thinking at the present time," said Dr. David Knopman, an Alzheimer's specialist at the Mayo Clinic in Rochester. Knopman, who describes himself as a friend and admirer of Ashe's, said that at this point, scientists "would be happy if we could forestall or slow down memory loss."

Nevertheless, the Mayo Clinic plans to work with Ashe to take her work "to the next stage," said Dr. Ronald Petersen, director of Mayo's Alzheimer's Disease Research Center.

He said her discovery could lead not only to future treatments, but to potential tests to identify patients at risk of developing dementia. "She's such a good scientist," he said. "I think there could be some definite clinical application to this work."

The advances, though, won't come fast enough for many patients and their families.

"You have to test it in animals first to make sure it works, make sure it's safe," she said, before even testing it on people. That's why, she said, even if all goes well, it will be years "before there would be a pill that you could get from the pharmacy."

Maura Lerner • 612-673-7384