Researchers reverse memory loss in mice

15/7/05. By the University of Minnesota

Researchers have reversed memory loss in mice with significant brain degeneration, a breakthrough that offers hope to 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 at the University of Minnesota and lead author of the study published in the 15 July 15 2005 issue of the journal 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.

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Professor Ashe and her team studied the effects of a mutant protein called tau. The researchers genetically engineered mice with a human gene - taken from a family with a high incidence of Alzheimer's - that produced 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, with the gene still turned on, underwent memory tests in a tank of water. Mice don't like water, so if a platform is put just below the surface, the mice will seek it out. And, once they learn the location of the platform, will look for it in subsequent trials even after it has been removed. As the normal mice aged, they remembered where the platform was and tended to swim in the part of the tank to find it. But the genetically engineered mice became forgetful and tended to swim randomly around the tank.

The researchers then gave the mice doxycycline to reverse the effects of the human tau-producing gene and they regained the ability to learn where the platform was and to look for it in the same part of the tank once it was removed.

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. Therefore, the researchers concluded, it is likely that tau is involved in memory loss and gain through some mechanism other than the formation of neurofibrillary tangles. The search for such an abnormal form of tau, and the process that forms it, may hold the key to treating Alzheimer's.

"We hypothesise that there's an abnormal tau causing the malfunction of the hippocampus, a brain structure necessary for proper formation and storage of memories," says Ashe. "If we find forms of tau causing the problems, we can find out how they are formed and try to block that process or the effects of the abnormal protein, or we can try to remove these proteins from the brain."

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.

Image crdit: Adrian Cousins

Researchers reverse memory loss in mice

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