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 goes through. The researchers further designed the mice so that the transgene that causes these symptoms could be "turned off." Transgenes are genes from one organism that have been incorporated into another organism.
The researchers predicted that when the transgene expressing the dementia was turned off, memory loss would stop. The results, however, surpassed their expectations. The mice's symptoms of dementia were reversed--in other words, they regained memory.
"Most Alzheimer's disease treatments focus on slowing the symptoms or preventing the disease from progressing, 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 brain or neural tissue," said Karen Ashe, professor of neurology and lead author of the study.
The results will be published in the July 15 issue of the journal Science.
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 fibers in neurons, and amyloid deposits, a toxic build-up of plaque in the brain. The researchers found that even after the memory loss was regained in the mice, the tangles remained, and even increased in number. This suggests that the tangles are not a cause of dementia as previously thought.
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 they can halt progression of the disease.
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.
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 gene expressing 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.
Researchers from the Department of Neuroscience at Mayo Clinic Jacksonville, and the Department of Neurology at Massachusetts General Hospital contributed to the study.