Sleep deprivation may increase the risk of developing Alzheimer's disease by raising the levels of tau proteins in the brain associated with the neurodegenerative disease.
Researchers at Washington University in the US found 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.
The findings, published 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 David Holtzman, a professor at Washington University.
"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," Holtzman said.
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.
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Recent research has shown that tau is high in older people who sleep poorly.
However, it was not 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 measured tau levels in mice and people with normal and disrupted sleep.
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, an assistant professor Washington University, 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 per cent, the researchers found.
Staying up all night makes people stressed and cranky and likely to sleep in the next chance they get. While it is hard to judge the moods of mice, they, too, rebounded from a sleepless day by sleeping more later.
To rule out the possibility that stress or behavioral changes accounted for the changes in tau levels, researchers created genetically modified mice that could be kept awake for hours at a time by injecting them with a harmless compound.
When the compound wears off, the mice return to their normal sleep-wake cycle -- without any signs of stress or apparent desire for extra sleep.
Using these mice, the researchers found that staying awake for prolonged periods causes tau levels to rise.
The findings suggest that tau is routinely released during waking hours by the normal business of thinking and doing, and then this release is decreased during sleep allowing tau to be cleared away.
Sleep deprivation interrupts this cycle, allowing tau to build up and making it more likely that the protein will start accumulating into harmful tangles.
In people with Alzheimer's disease, tau tangles tend to emerge in parts of the brain important for memory -- the hippocampus and entorhinal cortex -- and then spread to other brain regions.
As tau tangles mushroom and more areas become affected, people increasingly struggle to think clearly.
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