Findings were revealed in a study from the Washington University School of Medicine which suggests real life factors such as sleep may affect how fast the disease spreads. Sleep problems and AD are known to be associated in part via amyloid beta protein, but this study shows sleep disruption causes tau to increase rapidly and spread over time, as published in the journal Science.
Tau levels were measured in mice and humans with normal and disrupted sleep. Results showed mouse ISF tau was increased by up to 90% during wakefulness vs sleep and up to 100% during SD; human CSF tau increased over 50% during SD; in tau seeding and spreading model chronic SD increased tau pathology spreading; chemogenetically driven wakefulness in mice significantly increased ISF Aβ and tau. Lack of sleep alone is indicated in the findings to help drive the disease, and suggests good sleep habits may help to preserve brain health.
Even in healthy individuals tau is found in the brain, under certain conditions tau can clump together into tangles that injure nearby tissues and presage cognitive decline. WUSM research shows older people who sleep poorly have higher levels of tau, but whether lack of sleep directly forced levels upward or if they were associated in another way was not clear.
Mice are nocturnal animals, tau levels in fluids surrounding brain cells were found to be twice as high at night when they were more awake and active than during the day when they dozed more frequently; disturbing rest during the day caused daytime tau levels to double. According to Brendan Lucey, MD the same effect was seen in humans; after as sleepless night tau levels were found to increase by 50%.
Staying up made people cranky and stressed; while it is hard to judge mouse moods they also rebounded by getting more sleep later on. Mice were genetically engineered to be kept awake with a harmless compound to rule out possibility of stress or behavioral changes accounting for changes in tau levels, when the compound wore off the animals returned to normal sleep wake cycles without signs of stress or apparent desire for extra sleep. Staying awake for prolonged periods of time also caused tau levels to increased in the genetically engineered animals.
Taken together findings suggest tau is routinely released during waking hours, and is decreased during sleep allowing tau to be cleared away; sleep deprivation interrupts the cycle allowing tau to build up, making it more likely for the protein to accumulate and form harmful tangles.
Tau tangles tend to emerge in parts of the brain important for memory such as the entorhinal cortex and hippocampus and spread to other regions; as the spread and more areas become affected patients will increasingly struggle to think clearly.
Hippocampi of mice were seeded with small tau clumps to investigate whether spread of tau tangles is affected by sleep. One group of animals was kept awake for long periods of time and another group was allowed to sleep whenever they liked, after 4 weeks tau tangles had spread further in sleep deprived mice than in rested mice; and new tangles appeared in the same areas of the brain as affected in human with Alzheimer’s disease.
The brain needs time to recover from daily stresses, getting a good night sleep is very important. Although it is not known whether getting adequate sleep will protect against AD, it won’t hurt and this along with other data suggests it may even help to delay disease process if it has begun, says Holtzman.
Disrupted sleep was also found to increase release of synuclein proteins which are a hallmark of Parkinson’s disease; people with this disease also often have sleep problems.
