Study in mice, people explains why poor sleep linked to Alzheimer’s
From the WashU Newsroom…
Poor sleep has long been linked with Alzheimer’s disease, but researchers have understood little about how sleep disruptions drive the disease.
Now, studying mice and people, researchers at Washington University School of Medicine in St. Louis have found that sleep deprivation increases levels of the key Alzheimer’s protein tau. And, in follow-up studies in the mice, the research team has shown that sleeplessness accelerates the spread through the brain of toxic clumps of tau – a harbinger of brain damage and decisive step along the path to dementia.
These findings, published online Jan. 24 in the journal Science, indicate that lack of sleep alone helps drive the disease, and suggests that good sleep habits may help preserve brain health.
“The interesting thing about this study is that it suggests that real-life factors such as sleep might affect how fast the disease spreads through the brain,” said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “We’ve known that sleep problems and Alzheimer’s are associated in part via a different Alzheimer’s protein – amyloid beta – but this study shows that sleep disruption causes the damaging protein tau to increase rapidly and to spread over time.”
Tau is normally found in the brain – even in healthy people – but under certain conditions it can clump together into tangles that injure nearby tissue and presage cognitive decline. Recent research at the School of Medicine has shown that tau is high in older people who sleep poorly. But it wasn’t clear whether lack of sleep was directly forcing tau levels upward, or if the two were associated in some other way. To find out, Holtzman and colleagues including first authors Jerrah Holth, a staff scientist, and Sarah Fritschi, a former postdoctoral scholar in Holtzman’s lab, measured tau levels in mice and people with normal and disrupted sleep.
Mice are nocturnal creatures. The researchers found that tau levels in the fluid surrounding brain cells were about twice as high at night, when the animals were more awake and active, than during the day, when the mice dozed more frequently. Disturbing the mice’s rest during the day caused daytime tau levels to double.
Much the same effect was seen in people. Brendan Lucey, MD, an assistant professor of neurology, obtained cerebrospinal fluid – which bathes the brain and spinal cord – from eight people after a normal night of sleep and again after they were kept awake all night. A sleepless night caused tau levels to rise by about 50 percent, the researchers discovered.