Scientists at The Feinstein Institute for Medical Research have figured out why a substance in red grapes and red wine lowers amyloid beta levels that accumulate in the brains of Alzheimer’s patients. Medicines targeting amyloid beta that make up the clumps in the hallmark plaques are now in many phases of experimental testing. The hope is that clearing out amyloid beta before it accumulates could stave off the disease and reduce symptoms. Scientists at the Feinstein hope to develop this natural substance, called resveratrol, or synthetic versions, for the treatment of Alzheimer’s.
Valorie Vingtdeux, PhD and their colleagues have discovered that a specific kinase – AMPK – controls Abeta levels. AMPK is an interesting protein because it is a metabolic sensor in the cells and throughout the body. It senses levels of ATP, the body’s fuel source. When ATP levels drop, AMPK is activated to prepare the cells to adjust to the metabolic change in the body – when fuel is low. It’s like a driver moving along at 50 and slowing down when it realizes that there is trouble ahead.
Resveratrol activates AMPK and in turn this protein lowers Abeta levels. Dr. Vingtdeux presented these findings at the Society for Neuroscience annual meeting in Washington, DC, this week. The work has been done so far in cell culture but Philippe Marambaud, PhD, who oversees the research, said there is every reason to believe that a similar process takes place in nature. “We hope that this result will translate into beneficial effects for Alzheimer’s patients someday,” said Dr. Marambaud. This is an important finding because the scientists identified a new potential molecular target – AMPK – to lower Abeta levels in Alzheimer’s. It also opens the door to considering more potent analogs of resveratrol. Feinstein scientists are now screening libraries of substances to see whether there are any compounds that could mimic the effects found in this substance. As it is, the amounts found in grapes and wine are small and it would not be feasible to ingest enough to have a benefit. The Feinstein chemists have identified several compounds that are now in different stages of testing.
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