Sleep disruption increases Alzheimer’s-related protein levels

WASHINGTON – Disrupting deep sleep boosts the amount of an Alzheimer’s disease-related protein called amyloid-beta in the fluid bathing the brain and spinal cord, new research suggests.

And poor-quality sleep over time was associated with higher levels of tau, a different Alzheimer’s-associated protein, in the cerebrospinal fluid, Dr. Yo-El Ju of Washington University School of Medicine in St. Louis and colleagues found.

“The worse someone’s sleep quality, the more their amyloid beta and tau increase, and both amyloid beta and tau are involved in Alzheimer’s over the long-term,” Ju told Reuters Health in a telephone interview. “I don’t think people should worry about Alzheimer’s disease after one bad night. I do think chronic sleep disruption increases the risk of Alzheimer’s disease.”

Amyloid-beta and tau make up the plaques and tangles in the brain that are the hallmark of Alzheimer’s disease. Past studies have shown that amyloid beta levels drop during sleep and rise during wakefulness, and that just one night of sleep deprivation increases amyloid beta levels, Ju’s team writes in the journal Brain.

But it hasn’t been clear exactly what aspect of sleep disruption caused the build-up of the protein. They hypothesized that it was the interruption of slow-wave sleep - the deepest stage of dreamless sleep, when brain cells are at rest - because that is when amyloid-beta levels normally drop.

“Because brain cells release amyloid beta during activity, we think if the brain cells can’t rest the way they’re supposed to and get that deep sleep, they produce a relative excess of amyloid,” Ju said.

In the study, 17 healthy men and women aged 35 to 65 years took part in two sets of procedures, about a month apart. Both involved an overnight sleep study while wearing headphones, followed by a spinal tap in the morning to draw cerebrospinal fluid for analysis. In one sleep session, researchers monitored brain activity and when the person was entering slow-wave sleep, a tone was delivered through the headphones to prevent it. In the second session, slow-wave sleep was not interrupted.

The study team found that disrupted slow-wave sleep was followed by higher levels of amyloid-beta in cerebrospinal fluid in the morning.

“Tau takes much longer to get from the brain down to the lower back where the spinal fluid is measured, so for tau we looked at sleep in the preceding week as we had measured it with an actigraph,” Ju said. “We found that the worse the sleep quality in the preceding week, the higher the tau.”

The study doesn’t prove whether or how disrupted sleep contributes to the risk of developing Alzheimer’s disease. But Alzheimer’s is associated with disrupted sleep “in a bi-directional manner,” the researchers note, so the results shed light on one possible mechanism.

The team is now investigating whether treating obstructive sleep apnea - which is associated with multiple sleep interruptions each night, as well as an increased risk of Alzheimer’s disease and much earlier dementia onset - can reduce levels of amyloid beta and tau, and potentially Alzheimer’s risk.

“There are things that we can all improve upon to get the best sleep that we are capable of,” Ju said. “If someone suspects that they have sleep apnea, they should really seek evaluation and treatment.”

“This is yet another piece of information that suggests that sleep disruption certainly can be a risk for development of subsequent Alzheimer’s disease,” said Dr. Andrew Varga, a neuroscientist and neurologist at The Mount Sinai Integrative Sleep Center in New York City who studies sleep and Alzheimer’s.

The findings raise the question of whether improving sleep quality and increasing slow wave sleep, even in people without sleep disorders, could lead to lower levels of amyloid-beta and tau, and possibly slow or prevent the development of Alzheimer’s, said Varga, who wasn’t involved in the study.

While certain drugs and even sound stimuli have been used experimentally to promote slow-wave sleep, he noted, “not just the presence but the timing of the slow waves may be really important.” –Reuters