Alzheimer’s Scrambles the Metabolism-sleep Connection

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.

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. But a dip in blood sugar, caused by insulin injections, also led to more nerve cell action and more wakefulness.

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. Still, scientists caution 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.

CITATIONS C.M. Carroll et al. Aging and pathology cause sleep disruptions and altered metabolism in mouse models of Alzheimer’s disease. Society for Neuroscience annual meeting. October 23, 2019.