School of Medicine

Lack of sleep boosts levels of Alzheimer’s proteins

Study shows sleepless night taxes brain’s waste-disposal abilities

From the WashU Newsroom

Have you resolved to take better care of yourself in the new year? Here’s a relatively painless way to do it: Catch a few more zzz’s every night. A third of American adults don’t get enough sleep, according to the Centers for Disease Control and Prevention.

Chronic poor sleep has been linked to cognitive decline, and a new study from Washington University School of Medicine in St. Louis explains why: As a wakeful brain churns away through the night, it produces more of the Alzheimer’s protein amyloid beta than its waste-disposal system can handle. Levels of the protein rise, potentially setting off a sequence of changes to the brain that can end with dementia.

“This study is the clearest demonstration in humans that sleep disruption leads to an increased risk of Alzheimer’s disease through an amyloid beta mechanism,” said senior author Randall Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology. “The study showed that it was due to overproduction of amyloid beta during sleep deprivation.”

The findings are available online in Annals of Neurology.

More than 5 million Americans are living with Alzheimer’s, a disease characterized by gradual memory loss and cognitive decline. David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor of neurology, and Yo-El Ju, MD, an assistant professor of neurology, have shown that sleeping poorlyincreases levels of brain proteins such as amyloid beta that are linked to Alzheimer’s disease. But it wasn’t clear why amyloid beta levels rise in a tired brain.

Bateman, first author Brendan Lucey, MD, an assistant professor of neurology, and colleagues studied eight people ages 30 to 60 with no sleep or cognitive problems. The participants were assigned randomly to one of three scenarios: having a normal night’s sleep without any sleep aids; staying up all night; or sleeping after treatment with sodium oxybate, a prescription medication for sleep disorders. Sodium oxybate increases slow-wave sleep — the deep, dreamless phase of sleep that people need to wake up feeling refreshed.

Each scenario occurred during 36 hours of monitoring, starting in the morning and continuing through the afternoon of the following day. The researchers took samples of the fluid that surrounds the brain and spinal cord every two hours to monitor how amyloid beta levels change with time of day and tiredness.

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