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Memory Loss Reversed in Mice

14 July 2005 (All day)
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Brain tangles. A close-up of protein tangles in a mouse, which may not be responsible for memory loss, as previously thought.

Researchers have found a way to improve the impaired memory of mice with a condition similar to Alzheimer's. The finding suggests that tangled structures in the brain may not be causing the memory loss, which contradicts a widely-held theory about the basis of some memory disorders.

Twisted bundles of protein known as neurofibrillary tangles occur in the brains of people with Alzheimer's and other neurodegenerative diseases. Because the tangles occupy the hippocampus, a region responsible for memory, scientists have long thought the structures are related to memory loss. "People have assumed that these tangles are essentially the road towards neuron death," says Karen Ashe, a neurologist at the University of Minnesota in Twin Cities.

The first part of the experiment appeared to back this standard idea. Ashe and colleagues genetically modified mice so that production of a mutant form of the tau protein, an essential component of neurofibrillary tangles, could be turned on or off. When the researchers turned the mutant tau on, the mice formed tangles in their hippocampal regions. They also had poorer memory than control mice, forgetting the location of a hidden platform in a water maze.

But the next step yielded a surprise. To see if the memory loss could be reversed, the researchers turned off mutant tau production in the same mice. Tangles in these mice continued to grow, but the animals regained some of their lost memory, spending more time in the correct area of the maze. Ashe believes that the mutant tau protein may cause neurons to somehow fall "sick"--an effect that can be reversed by removing the protein. The tangles, she and her colleagues conclude in the 15 July issue of Science, are irrelevant to the memory loss.

"It is a remarkable finding with promising therapeutic implications," says Li-Huei Tsai, a neurobiologist at Harvard University in Cambridge, Massachusetts. But one must be cautious about transferring a mouse model to humans, warns Virginia Lee, a neurologist at the University of Pennsylvania in Philadelphia. One caveat, she points out, is that in Alzheimer's patients there is not an over-expression of mutant tau. Rather, the protein simply becomes more concentrated in neurons. "It's a provocative finding," she says, "but you can only extrapolate so much."

Related sites
Rats and mazes (including Morris Water Maze)
Ashe's home page

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