Sleep deprivation speeds up brain damage from Alzheimer's

Alzheimer's disease has long been linked to a lack of sleep, but researchers have little understood the cause of sleep disorders.

Researchers at the University of Washington School of Medicine in St. Louis, who are currently studying mice and humans, have found that sleep deprivation increases levels of key Alzheimer's protein. And, in follow-up studies in mice, the research team showed that insomnia accelerated the spread in the brain of toxic tufts of tau, an early warning sign of brain damage and a notch decisive on the path of dementia.

These results, published online January 24 in the newspaper Science, indicate that lack of sleep helps drive the disease and suggests that good sleep habits can help preserve brain health.

"The interest of this study is that it suggests that real factors, such as sleep, could affect how quickly the disease spreads in the brain," said David Holtzman, lead author, MD , professor to professor Andrew B. and Gretchen P. Jones, then head of the department of neurology. "We know that sleep problems and Alzheimer's disease are badociated in part with a different protein from Alzheimer's disease, beta-amyloid, but this study shows that sleep disturbances cause an increase in rapid tau protein, a harmful protein, and its spread over time. "

Tau is normally found in the brain – even in healthy people – but under certain conditions it can clump into an entanglement that damages nearby tissues and presages cognitive decline. Recent research at the Faculty of Medicine has shown that tau is high in older people who sleep poorly. But it was not clear whether lack of sleep directly forced tau levels to increase, or whether the two were badociated in some other way. To find out, Holtzman and colleagues, including lead authors Jerrah Holth, Ph.D., principal investigator and Sarah Fritschi, Ph.D., a former postdoctoral researcher at Holtzman's lab, measured tau levels in mice and people with normal and disturbed disorders. to sleep.

Mice are nocturnal creatures. The researchers found that tau levels in the fluid surrounding the brain cells were about twice as high at night, when the animals were more alert and active, than during the day, when the mice did not sleep anymore. frequently. The disruption of mice rest during the day doubled tau levels during the day.

The same effect has been observed in people. Brendan Lucey, MD, badistant professor of neurology, obtained the cerebrospinal fluid – which bathes the brain and spinal cord – in eight people after a normal night's sleep and again after having been awake all night. The researchers found that a sleepless night had resulted in an increase of about 50% in the tau.

Staying awake all night makes people stressed, cranky and likely to sleep at the next opportunity. While it's hard to judge the mood of mice, they also bounced back after a sleepless day sleeping later. To rule out the possibility that changes in stress or behavior are causing changes in tau levels, Fritschi has created genetically modified mice that could stay awake for hours as a result of injection. 39, a harmless compound. When the compound disappears, the mice resume their normal sleep-wake cycle with no signs of stress or apparent desire for additional sleep.

Using these mice, researchers found that staying awake for long periods of time increased tau levels. Overall, the results suggest that the normal task of thinking and doing frees the tau regularly during waking hours, and that this release decreases during sleep, which helps to rid it of tau. Sleep deprivation interrupts this cycle, allowing the tau protein to accumulate and increasing the risk of protein accumulation in harmful entanglements.

In people with Alzheimer's disease, tau tangles tend to appear in parts of the brain important for memory – the hippocampus and the entorhinal cortex – and then spread to other people. other areas of the brain. As tau mires mushrooms and more and more areas are affected, people are finding it increasingly difficult to think clearly.

To investigate whether the spread of tau tangles is affected by sleep, researchers seeded the mouse hippocampus with tiny tufts of tau and then kept the animals awake for long periods each day. A separate group of mice were also injected with tau entanglements, but were allowed to sleep when they wished. After four weeks, tau tangles had spread more in sleep-deprived mice than in their resting counterparts. Notably, new entanglements have appeared in the same areas of the brain affected by people with Alzheimer's disease.

"We should all try to have a good night's sleep," said Holtzman. "Our brains need time to recover from the stress of the day, and we do not know if, as we get older, people will get enough sleep to protect themselves from Alzheimer's disease." But that does not hurt, and other data suggest that help delay and slow down the disease process if it began. "

The researchers also found that sleep disturbance increased the release of the synuclein protein characteristic of Parkinson's disease. People with Parkinson's – like those with Alzheimer's – often have problems sleeping.

Provided by
University of Washington School of Medicine