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Alzheimers Patients Find Hope in Memory Restoration
in Mice
July 14, 2005 In another significant development
in the battle against Alzheimers disease, researchers at the University
of Minnesota were able to reverse memory loss in mice with significant
brain degeneration for the first time. It is a breakthrough that offers
hope to the estimated 4 million people living with Alzheimer's.
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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.
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