Brain cleanses Alzheimer’s plaques during sleep

Lack of sleep may contribute to Alzheimer’s disease by robbing the brain of the time it needs to wash away sticky proteins.

Neuroscientist Barbara Bendlin studies the brain as Alzheimer’s disease develops at the University of Wisconsin–Madison. When she goes home, she tries to leave her work in the lab. But one recent research project has crossed into her personal life: She now takes sleep much more seriously.

Bendlin and her colleagues identified 98 people from the registry who recorded their sleep quality and had brain scans. Those who slept badly — measured by such things as being tired during the day — tended to have more A-beta plaques visible on brain imaging, the researchers reported in 2015 in Neurobiology of Aging.

Plaques in the brain are a hallmark of Alzheimer’s, the most common form of dementia.

Bendlin’s studies are part of a modest but growing body of research suggesting that a sleep-deprived brain might be more vulnerable to Alzheimer’s disease. In animal studies, levels of plaque-forming A-beta plummet during sleep. Other research suggests that a snoozing brain runs the “clean cycle” to remove the day’s metabolic debris — notably A-beta — an action that might protect against the disease. Even one sleepless night appears to leave behind an excess of the troublesome protein fragment.

But while the new research is compelling, plenty of gaps remain. There’s not enough evidence yet to know the degree to which sleep might make a difference in the disease, and study results are not consistent.

A 2017 analysis combined results of 27 studies that looked at the relationship between sleep and cognitive problems, including Alzheimer’s. Overall, poor sleepers appeared to have about a 68% higher risk of these disorders than those who were rested, researchers reported last year in Sleep. That said, most studies have a chicken-and-egg problem. Alzheimer’s is known to cause difficulty sleeping. If Alzheimer’s both affects sleep and is affected by it, which comes first?

Approximately 1/3rd of U.S adults are considered sleep deprived (getting less than seven hours of sleep a night) and Alzheimer’s is expected to strike almost 14 million U.S. adults by 2050 (5.7 million have the disease today). The research has the potential to make a big difference.

Neurologist David Holtzman of Washington University School of Medicine in St. Louis thinks Alzheimer’s disease is a kind of garbage collection problem. As nerve cells, or neurons, take care of business, they tend to leave their trash lying around. They throw away A-beta, which is a leftover remnant of a larger protein that is thought to form connections between neurons in the developing brain, but whose role in adults is still being studied. The body usually clears away A-beta.

Sometimes, especially when cheated on sleep, the brain doesn’t get the chance to mop up all the A-beta that the neurons produce, according to a developing consensus. A-beta starts to collect in the small seams between cells of the brain, like litter in the gutter. If A-beta piles up too much, it can accumulate into plaques that are thought to eventually lead to other problems such as inflammation and the buildup of tau, which appears to destroy neurons and lead to Alzheimer’s disease.

Perhaps Alzheimer’s doesn’t just make it hard to sleep. Perhaps interrupted sleep drives the development of Alzheimer’s itself.

The central question — the one that doctors really want to answer — is whether better sleep could treat or even prevent Alzheimer’s. To try to figure this out, Bendlin and her Wisconsin colleagues are now studying people with sleep apnea. People with that condition stop breathing during the night, which wakes them up and makes for a lousy night’s sleep. A machine called a CPAP, short for continuous positive airway pressure, treats the condition.

“Once people start treatment, what might we see in the brain? Is there a beneficial effect of CPAP on markers of Alzheimer’s?” Bendlin wonders. “I think that’s a big question because the implications are so large.”

A study reported in Neurology in 2015 offers a reason to think CPAP might help. Using data from almost 2,500 people in the Alzheimer’s Disease Neuroimaging Initiative, researchers at the New York University School of Medicine found that people with sleep disorders like obstructive sleep apnea showed signs of mild cognitive problems and Alzheimer’s disease at younger ages than those who did not. But for those who used CPAP, onset of mild cognitive problems was delayed.

“If we find out that sleep problems contribute to brain amyloid — what that really says is there may be a window to intervene,” Bendlin says. And the solution — more attention to sleep — is one prescription with no side effects.