Alzheimer’s may scramble metabolism’s connection to sleep

Mice with signs of the disease respond abnormally to blood sugar changes

amyloid-beta protein

Sticky globs of amyloid-beta protein (brown in this illustration), a key sign of Alzheimer’s disease, alter how mice respond to changes in blood sugar, a study finds.

Selvanegra/iStock/Getty Images Plus

CHICAGO — Wide swings in blood sugar can mess with sleep. Food’s relationship with sleep gets even more muddled when signs of Alzheimer’s disease are present, a study of mice suggests.

The results, presented in a news briefing October 20 at the annual meeting of the Society for Neuroscience, show that Alzheimer’s disease is not confined to the brain. “Your head is attached to your body,” says neuroscientist Shannon Macauley of Wake Forest School of Medicine in Winston-Salem, N.C. Metabolism, sleep and brain health “don’t happen in isolation,” she says.

Along with Caitlin Carroll, also of Wake Forest, Macauley and coauthors rigged up a way to simultaneously measure how much sugar the brain consumes, the rate of nerve cell activity and how much time mice spend asleep. Injections of glucose into the blood led to changes in the brain: a burst of metabolism, a bump in nerve cell activity and more time spent awake. “It’s like giving a kid a lollipop,” Macauley says. “They’re going to run around in a circle.”

But a dip in blood sugar, caused by insulin injections, also led to more nerve cell action and more wakefulness. “You can have it go up high or go down low, and it was just really bad either way,” Macauley says.

Researchers did similar analyses in mice genetically engineered to have one of two key signs of Alzheimer’s. Some of these mice had clumps of amyloid-beta protein between nerve cells, while others had tangles of a protein called tau inside nerve cells.

Both groups of mice had abnormal reactions to high or low blood sugar. But those reactions depended on whether amyloid-beta or tau was in their brains. In mice with amyloid plaques, higher blood sugar led to a slight rise in brain metabolism, but not nearly as much as in a normal mouse. In mice with lots of tau, however, high blood sugar didn’t increase brain metabolism. In both cases, nerve cell activity no longer had big responses to blood sugar.

The two kinds of mice “respond to the same change in the blood sugar very, very differently,” Macauley says. A-beta and tau “might be affecting the sleep-wake circuit in very different ways, and we’re trying to understand that.”

Capturing this second-by-second action in mice brains is “beautiful work,” says neuroscientist Steve Barger of the University of Arkansas for Medical Sciences in Little Rock. The data “are really exquisite, in my opinion.”

Still, Barger cautions that mice don’t capture all aspects of Alzheimer’s disease. Some of the new findings come from mice engineered to make lots of A-beta quickly in their brains. That is “quite distinct from the way that most people get Alzheimer’s disease,” Barger cautioned.

But hints from humans also point to complex relationships between sleep and Alzheimer’s (SN: 8/16/19). Study coauthor David Holtzman, a neurologist and neuroscientist at the Washington University School of Medicine in St. Louis, has found that sleep begins to suffer in people with Alzheimer’s disease before other symptoms appear. Those results suggest that “sleep-wake centers and other parts of the brain are being damaged by Alzheimer’s pathology,” he says.

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