Scientists have discovered that in a mouse model, when the first signs of Alzheimer’s plaques appear in the brain, the normal sleep-wake cycle is significantly disrupted.
The Washington University researchers believe that if comparable sleep abnormities begin early in the course of human Alzheimer’s disease, the symptoms could provide early detection of the pathology.
“As we start to treat Alzheimer’s patients before the onset of dementia, the presence or absence of sleep problems may be a rapid indicator of whether the new treatments are succeeding,” said senior author David M. Holtzman, M.D.
The study is found in the journal Science Translational Medicine.
Holtzman’s laboratory was among the first to link sleep problems and Alzheimer’s through studies of sleep in mice genetically altered to develop Alzheimer’s plaques as they age.
In an earlier study, he showed that brain levels of a primary ingredient of the plaques naturally rise when healthy young mice are awake and drop after they go to sleep. Depriving the mice of sleep disrupted this cycle and accelerated the development of brain plaques.
A similar rising and falling of the plaque component, a protein called amyloid beta, was later detected in the cerebrospinal fluid of healthy humans studied by co-author Randall Bateman, M.D.
The new research shows that when the first indicators of brain plaques appear, the natural fluctuations in amyloid beta levels stop in both mice and humans.
“We suspect that the plaques are pulling in amyloid beta, removing it from the processes that would normally clear it from the brain,” Holtzman said.
Mice are nocturnal animals and normally sleep for 40 minutes during every hour of daylight, but when Alzheimer’s plaques began forming in their brains, their average sleep times dropped to 30 minutes per hour.
To confirm that amyloid beta was directly linked to the changes in sleep, researchers gave a vaccine against amyloid beta to a new group of mice with the same genetic modifications.
As these mice grew older, they did not develop brain plaques. Their sleeping patterns remained normal and amyloid beta levels in the brain continued to rise and fall regularly.
Scientists now are evaluating whether sleep problems occur in patients who have markers of Alzheimer’s disease, such as plaques in the brain, but have not yet developed memory or other cognitive problems.
“If these sleep problems exist, we don’t yet know exactly what form they take—reduced sleep overall or trouble staying asleep or something else entirely,” Holtzman said. “But we’re working to find out.”