Solving The Sleep & Alzheimer's Puzzle : Short Wave We know that people with Alzheimer's often have sleep problems. But does it work the other way? Do problems with sleep set the stage for this degenerative brain disease? Jon Hamilton introduces us to some scientists looking into that connection. In a recent study, researchers observed a key role deep sleep potentially plays in maintaining brain health and protecting the brain against Alzheimer's. Follow host Maddie Sofia on Twitter @maddie_sofia. Email the show at shortwave@npr.org.

Solving The Sleep & Alzheimer's Puzzle

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MADDIE SOFIA, HOST:

You're listening to SHORT WAVE from NPR. Maddie Sofia here with NPR science correspondent Jon Hamilton.

Hi, Jon.

JON HAMILTON, BYLINE: Hi.

SOFIA: So you are our in-house brain person.

HAMILTON: I do have a brain.

SOFIA: (Laughter).

HAMILTON: And on a good day, it even works.

SOFIA: OK. So you're here to talk to us about this puzzle that researchers have been trying to figure out about the connection between sleep and Alzheimer's disease.

HAMILTON: Exactly. So decades ago, scientists noticed that people with Alzheimer's often have sleep problems. They're awake more at night. They are often drowsy during the day.

SOFIA: Right.

HAMILTON: And the big question has been, does it work the other way?

SOFIA: So do problems with sleep set the stage for Alzheimer's?

HAMILTON: Right. Scientists have been trying to figure out how this could happen for most of a decade now. And just recently, they managed to add another piece to the puzzle. But to understand what they found, we need to dive into the mysteries of sleep and how it affects the health of our brain.

SOFIA: So today on the show, the connection between Alzheimer's and sleep. Can not getting enough sleep make the brain more vulnerable to this degenerative disease?

HAMILTON: And how sleep turns on this sort of dishwasher in the brain.

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SOFIA: OK, Jon. Scientists have been looking at this connection between sleep and Alzheimer's for a while, and a lot of these studies started in mice.

HAMILTON: Right. So several years ago, I stopped by this lab where they're doing research on mouse brains, and I met up with a scientist named Jeffrey Iliff.

JEFFREY ILIFF: Come on in.

HAMILTON: He's a brain scientist at the University of Washington now, but then he was studying mouse brains at Oregon Health and Science University.

ILIFF: Warning sign here because there's a very powerful laser in here that can actually blind you if you look into it.

SOFIA: Jon, doesn't that always make you want to look at it a little, like out of the side of your eye?

HAMILTON: Yeah. It's like the solar eclipse.

SOFIA: (Laughter).

HAMILTON: You kind of just can't help yourself.

SOFIA: I'm glad you didn't though.

HAMILTON: Anyway, the laser we're talking about made it possible for Jeff and his colleagues to study the brains of living mice using this state-of-the-art microscope.

ILIFF: So there's - black curtains surround this microscope because our microscope is very, very sensitive. And it's almost literally counting every single photon that comes up out of the mouse's brain.

SOFIA: Wow. So what are they using this fancy microscope to look at exactly?

HAMILTON: Well, to understand that, you kind of need to understand what happens in the brains of mice when they go to sleep.

SOFIA: All right. Mouse brain science, here we go.

HAMILTON: Right. When mice...

SOFIA: (Laughter).

HAMILTON: ...Sleep or for that matter, when people sleep, when you sleep, the brain cells shrink, so it's easier for this fluid to flow through the entire brain.

ILIFF: So what happens is during sleep, the fluid that's normally on the outside of the brain, which is called cerebral spinal fluid - it's a clean, clear fluid. It actually begins to recirculate back into and through the brain along the outsides of blood vessels. So it uses the blood vessels as sort of a scaffold allowing the - that CSF to exchange with the fluid between the brain cells.

HAMILTON: And that exchange between the CSF and brain fluid washes out all these toxins that build up during waking hours.

SOFIA: I've heard some scientists compare it to, like, how a dishwasher works - so getting rid of the dirty stuff that's accumulated on the plates, and the bowls and the silverware.

HAMILTON: It's not a bad comparison because that fluid can get going pretty fast. And by the way, the team that discovered it named it something. They call it the glymphatic system.

SOFIA: Sure, love it. OK, Jon, what kind of toxins are we actually talking about?

HAMILTON: OK. So brain cells, like all cells, produce waste that they need to get rid of - stuff like carbon dioxide, ammonia. And the cells kind of excrete this stuff. And it would build up in the spaces between cells if there weren't some kind of system that took it away.

SOFIA: Mmm hmm.

HAMILTON: So the scientists who discovered the system actually think these wastes are the reason that we can't think straight because we didn't get enough sleep.

SOFIA: That explains my brain since the launch of this podcast, Jon Hamilton (laughter).

HAMILTON: Oh, and animals and people eventually die without sleep.

SOFIA: Good to know (laughter).

HAMILTON: So at this point, you may be a highly functional zombie.

SOFIA: Yeah.

HAMILTON: But wait. Wait. There's more. By not sleeping, you also may be raising your risk for Alzheimer's. And the reason for that is that one of the waste products that builds up in the brain is something called beta-amyloid.

SOFIA: Beta-amyloid.

HAMILTON: Yeah. You've probably heard about the plaques and tangles that are associated with Alzheimer's disease. Well, beta-amyloid is the plaque.

SOFIA: OK.

HAMILTON: It forms these sticky clumps in the brains of people who either have Alzheimer's or are likely to develop it, and the idea is that beta-amyloid is part of a process that ultimately kills brain cells. So it was kind of alarming back in 2009 when scientists started finding evidence that a lack of sleep might actually be speeding up the development of these beta-amyloid plaques.

SOFIA: So basically, scientists found evidence of a strong connection between sleep - like, a lack of it can make your brain more vulnerable to Alzheimer's.

HAMILTON: Right, at least in mice, which really don't get Alzheimer's without some genetic tinkering.

ILIFF: So we have to find a way to see the same sort of function but in a way that is going to be, you know, reasonably noninvasive and safe for a human.

SOFIA: So have scientists figured out how to test for it in humans?

HAMILTON: Yep. And most recently, scientists have figured out a way to study it in real time.

LAURA LEWIS: My name is Laura Lewis. I'm an assistant professor of biomedical engineering...

HAMILTON: At Boston University - and Laura and a team of researchers found a way to watch the glymphatic system at work. This was in about a dozen sleeping people. The whole thing was written up in the journal Science. And what they did was have people fall asleep inside an MRI scanner, so in this cramped, like...

SOFIA: Yeah.

HAMILTON: ...Super noisy tube.

SOFIA: Not an easy place to nap.

HAMILTON: And then while these people were asleep, they used all this cutting-edge technology to monitor things like brainwaves and blood flow. And guess what, Maddie?

SOFIA: They saw the same thing that happened in mice - that lack of sleep can make people more vulnerable to Alzheimer's?

HAMILTON: Exactly. And they also used this really clever technique to watch the flow of this liquid that surrounds the brain and the spinal cord, and they found something that they hadn't really known before.

SOFIA: What did they find out, Jon?

HAMILTON: I'm going to let Laura describe it.

LEWIS: And that's when we discovered that during sleep, there are these really large, slow waves occurring maybe once every 20 seconds of CSF washing into the brain.

HAMILTON: So the fluid isn't just flowing steadily. It's kind of oscillating like a washing machine.

SOFIA: Hmm.

HAMILTON: And these researchers were watching this happen in a human brain, and then they saw something else - this other discovery.

LEWIS: Before each wave of fluid, we would actually see a wave of electrical activity in the neurons.

SOFIA: Whoa.

LEWIS: This electrical wave always happens first, and the CSF wave always seems to follow seconds later.

SOFIA: So were the electrical waves triggering the washing cycle that flushed out these toxins?

HAMILTON: Well, that is the current hypothesis.

SOFIA: OK.

HAMILTON: Those electrical waves are called slow waves, and they show up when a person enters a state known as deep sleep. So you know everybody talks about REM sleep...

SOFIA: Mmm hmm.

HAMILTON: ...Right? - rapid eye movement. This is a different state, and it's one where a lot of brain systems seem to be shut down. And people are a lot less likely to dream.

SOFIA: So the deep sleep thing is key here. The less somebody gets, the fewer slow waves, and the fewer the slow waves, the fewer the toxins flush out of the brain.

HAMILTON: That's what it looks like. And, of course, one of those toxins is beta-amyloid, that plaque we were talking about that's linked to Alzheimer's. And it looks like there's this kind of vicious cycle. You don't get enough sleep, so more beta-amyloid, you know, builds up...

SOFIA: Mmm hmm.

HAMILTON: ...In your brain. And when you build up beta-amyloid, it disrupts the sleep.

SOFIA: OK. So should an occasionally sleep-deprived podcast host or other people be worried about Alzheimer's if they're not getting enough sleep?

HAMILTON: Well, it's not quite that simple. There are a lot of things, not just sleep, that almost certainly contribute to the likelihood that somebody might get Alzheimer's. You have genetic factors.

SOFIA: Sure.

HAMILTON: There's something called the APOE four and three and two, which determine risk. There's also conditions like diabetes. Blood sugar in the brain is a factor. And then, of course, there's cell metabolism and how functional the cells are in your brain. All those things are factors, so it's not just sleep alone. But we know that getting sleep and getting the right kind of sleep is important for brain health for all sorts of reasons, and this is really just one more.

SOFIA: All right, Jon Hamilton. Good sleeping to you, sir. Thanks for coming by.

HAMILTON: You're welcome.

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SOFIA: Today's episode was produced by Brit Hanson and edited by Viet Le. I'm Maddie Sofia. Thanks for listening to SHORT WAVE from NPR.

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