Poor Sleep Causes Raised Levels of Tau in the Brain

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.

Link: https://medicine.wustl.edu/news/sleep-deprivation-accelerates-alzheimers-brain-damage/


Hello Reason! I have a degree in Pharmacy, and I've been working in a pharmacy in my town since then. Now I am thinking on becoming a scientist to study and reverse aging. What do you think I sholud study? Biology, biotechnology, medicine, ...?

Posted by: Josep at January 29th, 2019 6:01 AM

Not just what, where? It would be interesting to make an annual survey of the institutions doing the highly regarded papers in rejuvenation. In this, I'd like to help. Let's set up a set of criteria for the value of academic papers that various experts can weight. Then tag them with which one or more of the root causes of aging (on the right sidebar here) and the biological process or processes they address. Then invite the experts to score the papers on the criteria. Once you have a collection of scored papers, it would be trivial to create a "who's who" of both researchers, the fields they got their advance degrees in, the institutions that they got their degrees from, and where they did the work. It would be valuable information in making your choice.

If anyone has access to Science Citation Index, the would be a straight-forward process, other than getting experts to (probably anonymously) score the papers and weight the criteria.

Posted by: Tom Schaefer at January 29th, 2019 7:21 AM

@Josep: any pathway through the academic system that touches on medicine will get you to aging if you want to go that way. It is more a matter of picking the right advisors at later stages, and making connections and working with those groups doing something interesting.

Posted by: Reason at January 29th, 2019 2:35 PM

' Sleep appears necessary to clear out tau produced during waking hours, and loss of sleep means raised levels of tau persist. '

Alright, but what is the definition of poor sleep? Less than 7 hours per day? Do you need to sleep that much at once or do you just need to make sure you comcplete the sleep cycles? What is the definition here, completing sleep cycles, sleeping x hours, or what? How do we measure this accurately?

Posted by: Biological Realist at January 29th, 2019 8:34 PM

Hi Biological Realist! Just a 2 cents.

There was a study long while (forgot) where the graphic showed that 7 hours was the gold mean with the least mortality (I don't remember how they surveyed it, but it might have been in the population statistics surveys to death records). Children and toddles need more (8-16 hours); but once adult age or late teenage age happens, 7 hours a sleep each day, until natural death decades later. THey saw that increasing sleep over 7 hours also increases sudden death (in your sleep), sleeping too long is bad if done recurrently; if you are really tired and need more, like sleeping 12 hours straight, that's different, you need it and your circadian clock is asking for it; different. But, if you are not tired and just going to sleep like regular, you must get 7 hours. If you get 5-6 hours consecutively for many days (months or years), mortality/sudden death rises. It's incredible that just 1 or 2 and mortality rises (7 hours was the lowest point on mortailty bell shape curve graphic, above or under that, the curve rises).

Thus, yes the definition of poor sleep is less than 7 hours, mostly, but it can also mean more than 7 hours and feeling tired even after sleeping More (most likely fatigue/stress/exhaustion/need more sleep to recuperate all that you lose in daytime as you overwork yourself); it can also mean 'sleeping in bouts' 'waking up' in the middle of the night for peeing and then going back to sleep again.

On this particular point, the studies said that 'intermittent' awakening does not increase mortality substantially or not at all, as long as you get 'your 7 hours' whether -straight run uninterrupted (from to bed last night to next morning/waking up then only) or as intermittent bouts in the night (waking up several times during the night).

In my point of view, I don't think it's that great, you Want to Avoid that Absolutely if you can; because these intermittent bouts can mess up your circadian clock and also break the 'sleep stages' (NREM, REM dreaming stages of sleep), this can also make you have less 'time' in those stages that are crucial for recalibration of neuron/evacuation of tau/amyloid/junk/production of HGH/repair of tissues/tons of stuff happenign during sleep because circadian clock is activating the 'nocturnal gene program' if you will, a different one and only happening while asleep; if you don'T sleep well and wake up every 2 hours 'cutting your sleep' in little half-*ssed bits...bad.

You want a Long Strong Deep Sleep, from last night, all the way to the morning, uninterrupted, all the stages of sleep uninterrupted.

Centenarians, became centenarians, because they (have great genetics of course but besides that) kept a very 'boring/routine' routine with their sleep, meaning they Never sleep Less or More, than 7 hours every night...until they became a 100 years old. In fact, some are so strict with it...that they even went to bed on Their Birthdays..if the birthday party exceeded the time 'when it is to go to sleep'...so if that birthday party, film, whatever activity lasted until 1:00 AM in the morning..at 12:00AM they were gone and 'asleep' in their bed..they left the party and told others 'I have to go to sleep - right now. Goodbye'. In the next 5 minutes - they Will Fall Asleep. They do that because they wake up at 7:00AM sharp on the clock - each day..for decades and never changed that, ever. (some wake up earlier but go to be sooner to make up and obtain 7 hours) It is a military like-drill precision with them, and why they sleep so well and live this long. Early birds and 'routine-sleep-each night' increases chances of longevity.

That's to tell you how much sleep is crucial and staves off lots of problems, it might not make you live to a 100, but it gives that possibility when combined with great genetics (as in these (super)centenarians show).

The famed (or infamed) Chinese herbal botanist that took herbs to live forever, lived to the young age of 256 years old (there was just a small typo on that '256' year old passport of his (later was debunked hoax), he said:

''Walk light like dove, move slowly like a turtle and sleep like a dog'' (he lived to about 115-120s, from his pictures). (Dogs sleep well, his words are true, except the part that he tried to convince others he was 250some years old...give or take in his old memory/wanted to have fame and why centenarians know they are rare/cam make dough from being rare (though I don't mean in a bad way, it's just true...centenarians are rare, but not so rare anymore, more people reach that age; but supercentenarian that is Very rare (110-115 club, and 120 club is non-existent, for in 5 years death is exponential around 115-120 bracket).

Just a 2 cents.

Posted by: CANanonymity at January 30th, 2019 2:56 AM
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