Researchers here suggest a possible explanation for the observed association between disrupted sleep in later life and the development and progression of Alzheimer's disease. Sleep appears necessary to clear out tau produced during waking hours, and loss of sleep means raised levels of tau persist. The more tau in circulation, the more that an altered form of tau will be generated and aggregate into neurofibrillary tangles to damage brain cells. More research would be needed to quantify the size of this effect in comparison to, say, the contributions of lack of exercise or obesity. In the long run, however, one would hope that therapies capable of safely and efficiently clearing neurofibrillary tangles will make the whole question of contributions of this nature entirely irrelevant.
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 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.
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 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, researchers 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 rest during the day caused daytime tau levels to double. Much the same effect was seen in people.
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. Using these mice, the researchers found that staying awake for prolonged periods causes tau levels to rise. Altogether, 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.