A new study from researchers at Washington University School of Medicine in St. Louis has revealed further evidence of how sleep deprivation can drive the spread of toxic Alzheimer's-inducing proteins throughout the brain. The study bolsters the growing hypothesis suggesting sleep disruption plays a major role in the progression of neurodegenerative disease.
Over the last year or two there have been several notable studies published investigating how poor sleep seems to be fundamentally linked to neurodegenerative diseases such as Alzheimer's. Prior work has clearly demonstrated how just one night of disrupted sleep can increase accumulations in the brain of a protein called amyloid-beta, one of the central pathological drivers of Alzheimer's disease.
Now sleep researchers have turned their focus towards the other major toxic protein often implicated in Alzheimer's pathology – tau. Alongside the amyloid clumps, often hypothesized to be the driver of Alzheimer's-induced brain damage, tau proteins are also implicated as being damaging. These abnormal tau clumps, called neurofibrillary tangles, are often identified in neurodegenerative disease.
A recent study from the Washington University School of Medicine in St. Louis revealed higher levels of tau proteins were identified in human subjects who reported disrupted sleep patterns. It was unclear from that research whether the sleep disruptions preceded or followed these pathological brain changes. Now, a new study from the same team has revealed strong evidence suggesting sleep disruption does indeed directly cause tau protein levels to rise and more rapidly spread through the brain.
The new research describes several experiments, in both mice and humans, that clearly establish tau levels rising as a result of sleep deprivation. Tests in humans revealed a single sleepless night correlated with tau levels in cerebrospinal fluid rising about 50 percent. These results were also observed in mouse models subjected to extensive stretches of sleep deprivation.
The researchers also investigated whether sleep deprivation accelerates the spread of toxic tau neurofibrillary tangles. Two groups of mice were seeded with neurofibrillary tangles in their hippocampi, with one group allowed to sleep according to normal patterns, while the other group was kept awake for long periods every day.
After four weeks, the mice subjected to sleep deprivation showed significantly greater spread and growth of the tau tangles, compared to the well rested animals. These increased neurofibrillary tangles were also found in brain areas similar to those seen in human subjects suffering from Alzheimer's disease.
"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," says David Holtzman, senior author on the new study. "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."
Despite the robust research described in the new study, there are still several limitations to how the conclusions can be interpreted. For example, it is unclear how long-lasting these tau spikes actually are. Does a good night's sleep clear out the increased amyloid and tau load caused by a bad night's sleep? Does this even play a major role in the slow, long-term onset of diseases such as Alzheimer's? There is growing debate over whether tau and amyloid are even the right targets for understanding the pathogenic origins of Alzheimer's disease.
Holtzman is open about the limitations of his research, however, he suggests if the outcome is that people try to pay more attention to their sleep cycles then that will undoubtedly be beneficial.
"Our brains need time to recover from the stresses of the day," says Holtzman. "We don't know yet whether getting adequate sleep as people age will protect against Alzheimer's disease. But it can't hurt, and this and other data suggest that it may even help delay and slow down the disease process if it has begun."
The new study was published in the journal Science.
Source: Washington University School of Medicine in St. Louis
