
Lack of sleep boosts levels of Alzheimer's proteins - dnetesn
https://medicalxpress.com/news/2017-12-lack-boosts-alzheimer-proteins.html
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DrScump
Blogspam of

[https://medicine.wustl.edu/news/lack-sleep-boosts-levels-
alz...](https://medicine.wustl.edu/news/lack-sleep-boosts-levels-alzheimers-
proteins/)

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Nomentatus
But remember that the largest effects are from darkness, not sleep per se.
True darkness (can't see your hand), at very regular times and long enough to
create biphasic sleep. Red light doesn't trigger ipRGCs, and melatonin leads
garbage clean up in mitochondria.

~~~
perl4ever
That's interesting, because I've acquired an aversion to having the light off
when I sleep. For some reason it doesn't inhibit me from falling asleep with
it on any more and while I can sleep with it off, it doesn't feel quite right
somehow. I also have developed irregular sleep patterns, spending anywhere
from 5 to 22 hours awake, and 8-10 asleep.

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manmal
Alcohol also doesn’t inhibit one from falling asleep (on the contrary), but
sleep phases are messed up. I feel quite rested after one night with alcohol,
but things fall apart after 2-3 consecutive nights.

What I mean is.. if I were you, I would try sleeping in pitch black for a week
and then check how I‘ve adjusted.

~~~
dzhiurgis
Alcohol screws you up in long term - try some valerian - it produces the same
hormone that makes you fall asleep on booze GABA.

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Apocryphon
In recent weeks if not months, HN has been my go-to "fret about getting
Alzheimer's/dementia" newsfeed.

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davidw
Has it come up here before? I don't really recall.

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Apocryphon
Search turns up way more, but these were the recent stories that came to mind:

[https://news.ycombinator.com/item?id=15978252](https://news.ycombinator.com/item?id=15978252)
[https://news.ycombinator.com/item?id=15477048](https://news.ycombinator.com/item?id=15477048)
[https://news.ycombinator.com/item?id=15508714](https://news.ycombinator.com/item?id=15508714)

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eweise
I think that was a joke.

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hendry
This video lecture by Professor Matthew Walker is great to learn more on the
importance of sleep:
[https://www.youtube.com/watch?v=aXflBZXAucQ](https://www.youtube.com/watch?v=aXflBZXAucQ)

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spjwebster
I can highly recommend the book - Why We Sleep - mentioned at the top of the
video. It goes into quite some depth on the reasons for and mechanics of sleep
in a way I found approachable for someone with only a layman's understanding
of chemistry:

[https://www.amazon.com/dp/1501144316](https://www.amazon.com/dp/1501144316)

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db48x
Of course we still don't actually know if amyloid beta causes Alzheimer's, or
if it's just another symptom.

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fnayr
I wonder how the protein collects in people like myself, who will routinely
stay up 24-30 hours, but then sleep 12-14 hours after.

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pishpash
It says in the article, clearing away happens at the same rate, but production
happens at a higher rate when awake. Your peak concentration of this protein
will be higher, thus causing more damage. This seems to indicate that frequent
naps and polyphasic sleep may be good.

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fnayr
But if the rate of clearage is the same then because I’m sleeping longer it
should clear more of the protein?

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yorwba
The amount of harmful protein cleared is likely proportional to the product of
concentrations of the harmful protein and the clearing protein, because the
two need to interact. That means that clearing becomes slower as less harmful
protein is left.

Prolonging the clearing process would mean that you spend a longer time at
very low concentration, but not that the minimum concentration would be much
lower. If the harm of high concentrations is disproportionally higher, the
longer time at lower concentration would be unable to balance that out.

However, this is only based on my rough intuition and I didn't even do any
napkin math. If you want to really get a quantifiable comparison, you'd better
find out about the concrete interactions in question and calculate it
yourself.

Or you could ask a physician who specializes in sleep (I forget what they are
called), but if it isn't already published science somewhere, it's unlikely
they could tell you anything other than that what you're doing is highly
unusual and you should probably stop.

~~~
fnayr
Thanks for the intuition. We're done very soon and hope to never go this hard
again.

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QAPereo
It’s worth pointing out that while b-amyloid and tau proteins are _suspected_
of playing a crucial role in Alzheimer’s, disease it isn’t actually confirmed.

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joveian
It is hard to tell from this article, but looking at the paper the key thing
they were focusing on is the mechanism for the previously observed diurnal
variation in amyloid beta. They do some modeling that they say suggests that
the main factor allowing levels to decrease at night is reduced production
rather than increased clearance. One implication of this is "Given that there
are many approved therapies targeting sleep, the effect of sleep-inducing
drugs on CSF Aβ should be tested in individuals with sleep disruption and
promising candidates investigated in AD prevention trials."

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dzhiurgis
I keep wondering how much impact cannabis has.

I recently found out that it inhibits REM sleep, which really starts to feel
after few months being stoned. The worst part is coming back from it - the
dreams are extra vivid.

Now the article mentions long-wave sleep being the cause tho, but I can’t help
to think that constant REM sleep deprevation has to have some sort of impact
in the long term, perhaps we haven’t discovered it yet.

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polskibus
Is this process helped by taking melatonin?

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superobserver
Given that the etiology of Alzheimer's is tied to the very same proteins that
must be cleared out during sleep, and that the requirements of sleep decrease
with age, there seems to be a cyclical feedback loop at play here, insofar as
healthy aging does not typically difficulties with R&R. (This example becomes
more salient in the case of supergenarians who can rest and let little stress
them a great deal.) Compound that with a likely immunodeficient response
during sleep (where the brain is supposed to become more spongy) for these
proteins to be cleared out and a poorly functioning blood-brain barrier, it
would seem finding treatments that focus on these self-restorative responses
would be most beneficial. Whereas treatments that temporarily boost processing
capabilities will only somewhat delay the onset clearly shows that this is
most likely the case.

I wonder what study on general EEG signatures may reveal with respect to the
efficiency with which the cleanup process can be facilitated thereby. Perhaps
meditative practices could be demonstrated as a form of protein-cache clearing
even when in a waking, albeit altered, state of consciousness.

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joveian
It sounds like production is the key here not clearance but I am also
interested if meditation affects that. I did a quick search and didn't see
anything.

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chiefalchemist
To be clear, afaik, the lack of sleep doesn't increase levels; sleep lowers
levels, as sleep is the body's / brain's recovery process.

~~~
joveian
It looks like they are saying the opposite, that the lack of sleep does
increase levels.

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chiefalchemist
Waking ups levels. Sleep lowers them. This is the natural cycle/process.
Remove sleep and yes levels will increase. But the cause isn't being awake,
it's the lack of sleep. Yes?

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joveian
My understanding is that they are saying that the cause is being awake. I
don't understand the modeling they are doing, but they are saying that the
time curve of the concentration should be different if clearance was changing
at night, so they think there is little change in clearance but only in
production.

They mention one alternative that would also fit the data: "In order for
decreased glymphatic clearance during sleep deprivation to increase soluble
CSF Aβ, a decrease in irreversible losses (e.g. to the bloodstream or
lymphatics) due to prolonged overnight waking would have to be perfectly
matched by an increase in Aβ clearance to CSF. This is plausible but unlikely
and not identifiable from the current data."

They say "The SILK kinetics results unequivocally show that glymphatic
clearance alone, without compensation from other clearance mechanisms, would
be ineffective in protecting the brain from AD because overall clearance rates
are not changing. Glymphatic clearance may potentially contribute to the
protective effects of sleep against AD, but changes in production rate seem to
be the necessary and critical factor."

Also worth noting that they were unable to test if changes in slow wave sleep
made a difference because sodium oxybate didn't actually increase slow wave
sleep in that group vs normal sleepers.

It does sound like this contradicts previous research, at least:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880190/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880190/)

They do cite that paper but do not have a detailed analysis of how their
results could be consistant or are contradictory to what that study found. In
that study radioactive amyloid beta was directly injected into mice and then
how much of it was left was observed after varying amounts of time later and
in sleeping vs. awake vs anesthetized. Maybe newly produced amyloid beta could
be cleared instead of the radiolabeled amyloid beta or maybe the injected
amyloid beta had different clearanace properties than naturally generated
amyloid beta, but I don't know if either of those are plausable. Maybe they
are just contradictory results.

If it is correct that the production changes are what makes the difference, I
wonder why that is the case considering the much larger fluid exchange that
happens at night. Also I wonder if some of the other similar substances that
cause problems if they accumulate too much have a similar issue. Maybe stuff
that can be cleared at high rate is easier to get rid of with relatively
little sleep and stuff that can't is more likely to cause trouble over time.

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waytogo
That lacking sleep creates all kinds of disease is no surprise. The question
is _how_ to get sleep.

~~~
overcast
The answer is going to sleep, at a regular time. Put down the computer, put
down the cell phone, put down the games. Go to bed early. Above all else I
make sure I get my eight hours every night. If I'm tossing and turning, I'll
call into work. As a result, I am NEVER sick. Ever. Anecdotal sure, but if I
don't get sleep, I feel like I'm coming down with something.

Also naps, take advantage of them. I'll often go home on lunch, and take a
snooze for an hour.

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ianai
Reads like a commercial for Sodium oxybate. Also makes me want to further hone
in on my sleep.

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thats_right
Is this why living life according to a stupid fucking alarm clock, where I
have to blast my ears with noise at 6AM, to snooze until I actually get out of
bed at 7AM every morning, be out the door by 8AM, and wade through shitty
commuter traffic until 9AM, makes me want to stab people?

I honestly am not worth talking to before 11AM, and I need at least half an
hour to settle in and check emails. Oh, you’re taking lunch at noon? Good for
you. See you at 1PM. I don’t care. I’ll stay until 8PM. Just give me my
mornings back, please?

Why the fuck am I in 10AM meetings? Why are people awake at 9AM? I have to
drink a gallon of coffee to make it to 5PM, and that fucks my shit up until
2AM. I fucking hate all of you.

