U researchers reverse memory loss in mice

Karen Ashe and her Alzheimer's research mouse

By Deane Morrison

From M, fall 2005

For the first time, researchers at the University of Minnesota were able to reverse memory loss in mice with significant brain degeneration, an advance that suggests the same thing may be possible--at some point in the future-for the estimated 4 million people living with Alzheimer's disease.

"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," says Karen Ashe, professor of neurology and lead author of the study published in the July 14 issue of Science.

The study also produced strong evidence that twisted bundles of protein tangles--once thought to produce memory loss--are not the culprits. Instead, mutant proteins, not the tangles themselves, may be working like poisons to disrupt brain function.

The researchers genetically engineered mice with a human gene--taken from a family with a high incidence of Alzheimer's--that produced a mutant protein called tau. The mice also were outfitted with a molecular switch that could turn off the gene when the animals were fed a drug, doxycycline.

The mice underwent memory tests, and Ashe and her team found that turning on the gene caused memory loss. By turning off the tau gene in the mice, memory was restored, yet their brains continued to accumulate neurofibrillary tangles, once considered the cause of Alzheimer's symptoms.

Ashe cautions that results in mice often do not translate into humans and that doxycyline could not help humans because they are not genetically engineered, as the mice are, to turn off genes in response to the drug. But because this study involves the manipulation of a human gene, hopes are high that the research will one day translate into helping those who suffer from Alzheimer's.

The study was funded by the National Institutes of Health and the Edmund Wallace and Anne Marie Tulloch Chairs in Neurology and Neuroscience, which are held by Ashe.