Karen SantaCruz of the University of Minnesota and her colleagues genetically engineered mice to experience symptoms similar to those seen in humans with Alzheimer's disease--notably brain atrophy and associated memory loss that worsened over time. The mutant gene responsible for the brain damage, called tau, was modified such that it could be deactivated in the animals using medication. To gauge the effects of the disease over time, the researchers trained the animals to locate a submerged platform in a tank of water. When placed in the pool, the animals would swim to its location, even after it had been removed. But as their dementia progressed the animals forgot where they expected the platform to be and began paddling aimlessly around the water instead. The scientists hypothesized that when the effects of the overactive tau gene were removed, the animals' memory loss would stop. In fact, when the dementia-causing gene was deactivated, not only did their memories no longer degrade, but they began to improve. The mice once again began to concentrate their searches in the correct area of the pool, suggesting they had recovered memories of their training sessions.
In humans, two different substances that accumulate in the brain are implicated in Alzheimer's: twisted neurofibrillary tangles, which include tau proteins, and amyloid deposits comprised of toxic plaque build-up. For the study mice, after the mutant tau gene was dampened and some memory regained, their neuron numbers stabilized but the tangles remained. The tangles themselves may therefore not be responsible for causing memory problems, at least in mice. The research gives scientists a new model to test potential therapies, but the work is not immediately applicable, because it is not feasible to simply turn genes on and off in people. "Most Alzheimer's disease treatments focus on slowing the symptoms or preventing the disease from progressing," remarks study co-author Karen Ashe of the University of Minnesota, "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."