Yo-El Ju

One experiment that we did in my lab to really drill down into which specific part of sleep is linked to amyloid

is we did a study where people came in and spent two nights, at least a month apart, and we set up a closed-loop system where, you know, after they fell asleep, we were reading their brain waves, and there was an automated system where once they started getting into deep, slow-wave sleep, they would get a little beep through headphones.

And this beep would get louder and louder and louder every 10 seconds until it nudged them out of deep sleep into lighter sleep, not waking them up fully.

And we did that one night.

And then on a different night, we did a sham condition where we did not deprive their slow-waste sleep.

And what we found out in that study is that when we look at the spinal fluid levels of amyloid, which we measure through lumbar punctures the next morning,

there's a very specific correlation between how much we're able to suppress slow-wave sleep and how much amyloid beta increases.

So there seems to be this very specific link between soluble amyloid beta and slow-wave sleep.

That's not to say other stages of sleep aren't important.

They are.

REM sleep is very important for memory formation, for emotional regulation, and so on.

But when it comes to the actual...

amyloid beta levels, it seems like slow-wave sleep is the main part of sleep we should be concerned about.

I don't know if anyone has done the specific slow-wave sleep disruption.

Yeah.

There are, tau phosphorylation is affected by, for example, giving a drug to increase sleep, not necessarily slow-wave sleep, but DORA, which is a dual orexin receptor antagonist.

There was a human study here done by Brendan Lucey and colleagues where they gave people that drug, and that seemed to alter the phosphorylation of tau measurable in the plasma.

In the slowly sleep deprivation experiment, we do have plasma and CSF, obviously, from the next day, but we have not tested the different plasma.

Well, I guess I would add mortality to that as well.

So all plasma mortality is linked with sleep regularity and duration as well.