A drug that restores brain metabolism in mouse models of Alzheimer’s also improved cognitive function. The discovery could help researchers find additional pathways to combating the symptoms of this brain disease, beyond the telltale amyloid plaques and tau tangles that are hallmarks of Alzheimer’s.
ARI SHAPIRO, HOST:
Scientists are experimenting with a novel approach to treating Alzheimer’s disease in mice. They’re using a drug that helps the brain make energy. NPR’s Jon Hamilton says in a mouse, at least, the treatment can reverse memory loss.
JON HAMILTON, BYLINE: The brain is powered by sugar in the form of glucose. And in a young, healthy person, brain cells are really good at transforming glucose into energy. But Dr. Katrin Andreasson of Stanford University says in someone with Alzheimer’s…
KATRIN ANDREASSON: The energy metabolism really tanks. It really drops.
HAMILTON: So Andreasson and a team of scientists did an experiment with mice that develop a form of Alzheimer’s. They altered the animal’s genes in a way they thought would make glucose metabolism even worse and, as a result, accelerate the disease.
ANDREASSON: We expected to see everything much, much, much worse. But, no, it was the complete flip opposite.
HAMILTON: Eventually, the team found an explanation. The genetic tweak had altered the behavior of cells called astrocytes. Usually, these cells help provide energy to neurons, the cells involved in memory and thinking. But Andreasson says when Alzheimer’s plaques and tangles begin to appear in the brain, astrocytes stop doing this job.
ANDREASSON: The astrocytes are kind of put to sleep, but you got to wake them up, you know, to get them to help the neurons.
HAMILTON: The genetic tweak seemed to get the astrocytes back on track. To test that idea, the team did another experiment. Andreasson says they would place a mouse in the center of a shiny, white disc under a bright light.
ANDREASSON: It really doesn’t like it. It wants to get out of there, but it has to learn where the escape hole is.
HAMILTON: By following visual cues. Andreasson says healthy mice learned how to find the exit almost instantly.
ANDREASSON: But in the Alzheimer mice, the time to find the escape hole really skyrocketed.
HAMILTON: Until the team gave those mice an experimental cancer drug. It woke up the astrocytes the same way the genetic tweak had. It also restored normal glucose metabolism in the hippocampus, an area that’s critical to memory and navigation. And once a mouse had been treated, it could escape the bright light as quickly as a healthy animal. Another experiment showed that the drug also restored human astrocytes and neurons derived from Alzheimer’s patients. The results appear in the journal Science, and Shannon Macauley of the University of Kentucky says they show that Alzheimer’s involves a lot more than just plaques and tangles.
SHANNON MACAULEY: The thought that we can have these metabolic changes in our brain but they’re reversible, to me, is a very exciting development and can kind of change how we think about targeting this disease.
HAMILTON: Macauley, who wrote an editorial accompanying the study, says the research adds to the evidence that cells other than neurons play an important role in Alzheimer’s. She says the brain is a bit like a beehive. Neurons may be the queen bees, but they’re kept alive by worker bees like astrocytes.
MACAULEY: And those worker bees are getting unbelievably taxed from all the things that they’re being asked to do, and so when that happens, the whole system doesn’t work well. And I think that’s what’s happening kind of in the Alzheimer’s brain.
HAMILTON: Macauley says treatments aimed at those worker bees could eventually help Alzheimer’s patients, including those who are already taking new drugs that remove amyloid plaques. She says amyloid drugs can slow down the disease, but a metabolic drug might actually reverse some symptoms.
MACAULEY: Maybe this can make your astrocytes and your neurons work a little bit better so that you can function a little bit better. Maybe you can plateau those memory declines or get a little executive function back.
HAMILTON: If the approach works in people, she says, not just mice.
Jon Hamilton, NPR News.
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