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Scripps Researchers Find Culprit in Alzheimer’s-Related Brain Damage

Franck Polleux, a Scripps Research Institute neuroscientist, led a new study that implicates the enzyme AMPK in brain damage typically seen during the onset of Alzheimer's disease.

Franck Polleux of The Scripps Research Institute in La Jolla has been studying Alzheimer's disease for the last two and half years. He's also been studying type 2 diabetes—he just didn't know that at first.

This week, Polleux and his colleagues published a study in Neuron that could have important implications for the treatment of both diseases.

The researchers found that, at least in mice, overactivation of a particular enzyme leads to the kind of brain damage typically seen during the early stages of Alzheimer's disease. They show that blocking overactivation of this enzyme, called AMPK, can prevent such damage.

That could be good news for Alzheimer's drug research, but bad news for diabetics.

That's because the most common prescription for type 2 diabetes—a drug called metformin—ramps up activation of AMPK. Type 2 diabetes has long been considered a risk factor for Alzheimer's, and Polleux thinks metformin might be the link.

"We have direct evidence that metformin overactives AMPK in neurons, and that is toxic to neurons," he said.

Until clinical trials can be done on metformin and AMPK activation, Polleux said diabetics should continue taking the drug. But he believes these findings send out a "warning call to reevaluate how innocuous it is."

Scripps researchers plan to investigate what these findings mean for Alzheimer's drug development.

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