Researchers reverse memory loss in mice

Thursday, July 14, 2005

JACKSONVILLE, Fla., July 14, 2005 — Researchers at Mayo Clinic, the University of Minnesota and Massachusetts General Hospital were able for the first time to reverse memory loss in mice with significant brain degeneration, a breakthrough that offers hope to the estimated 4 million people living with Alzheimer's disease.

Researchers first manipulated the genetic makeup of the mice so they developed dementia. The mice experienced memory loss that worsens over time and had brain atrophy similar to what a person with Alzheimer's disease develops. The researchers further designed the mice so that the tau transgene that causes these symptoms could be "turned off." Transgenes are genes from one organism that have been incorporated into another organism, such as a human gene placed in a mouse.

"We wanted to determine if we could halt the progression of the disease," says Jada Lewis, Ph.D., assistant professor of neuroscience at Mayo Clinic in Jacksonville. "That's important, because it would tell us whether we could stop memory problems from getting worse in patients once we find a therapy." Mayo scientists helped develop the mouse models used in the studies.

The results surpassed the researchers' expectations. Once the human tau transgene was turned off, the mice's symptoms of dementia were reversed — in other words, they regained memory despite having neurodegeneration similar to that seen in Alzheimer's disease patients. The results will be published in the July 15 issue of the journal Science.

"Most Alzheimer's disease treatments focus on slowing the symptoms or preventing the disease from progressing," says Karen Ashe, professor of neurology at the University of Minnesota and lead author of the study. "But our research suggests that in the future we may be able to reverse the effects of memory loss, even in patients who have lost some brain or neural tissue."

In the past, it was generally accepted that dementia was caused by two substances that accumulate in the brain: neurofibrillary tangles, which are tangled bundles of tau protein in neurons, and amyloid deposits, a buildup of plaque in the brain. The researchers found that even after the memory loss was regained in the mice, the tangles remained and actually increased in number. This suggests that the tangles are not a cause of dementia as previously thought.

The study measured the mice's spatial memory through a water maze — a pool of water with a submerged platform. The use of this maze taps into the hippocampus, an area of the brain important in Alzheimer's disease research because of the role it plays in memory.

Since mice are not fond of water, they will swim to find the platform. First the mice were put in the pool and allowed to learn where the platform is located. After they learn where the platform is, the platform is removed, and the mice are again put in the pool. The researchers measured how much time the mice spent swimming in the area where the platform should have been.

Since the mice were designed to develop dementia, over time they forget where the platform should be and swim aimlessly around the pool. After the researchers turn off the transgene causing the memory loss, the same mice that swam aimlessly around the pool would again concentrate their search on the area of the pool where the platform was located, thus showing memory recovery.

The mice serve as a model that shows how the disease progresses as well as the possibility that memory loss can be reversed. The research suggests that the same reversal may be possible in humans, and that people with Alzheimer's disease may be able to recover memory and improve in cognitive function if disease progression can be stopped.

"The next step is to understand how brains of mice are able to rebound in the face of this degeneration and to determine whether there's a therapy that could work this way in people," Lewis says. "Our goal is to find a drug or treatment to help mid- or late-stage patients who don't show any benefit from current therapy. The results of this study give us hope for a treatment."

For more information, contact:

Mayo Clinic
Erik Kaldor
(904) 953-2299
kaldor.erik@mayo.edu

University of Minnesota
Sara Buss
(612) 624-2449

— 30 —

Mayo Clinic is a multispecialty medical clinic in Jacksonville, Fla. The staff includes 310 physicians working in more than 40 specialties to provide diagnosis, treatment and surgery. Patients who need hospitalization are admitted to nearby St. Luke's Hospital, a 289-bed Mayo facility. Mayo Clinics also are located in Rochester, Minn., and Arizona. Visit www.MayoClinic.org/news for all the news from Mayo Clinic.

###

To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. MayoClinic.com is available as a resource for your health stories.