For her new research on the brain’s plumbing system, neuroscientist Maiken Nedergaard had to hone many techniques. Among them — coaxing her lab mice into restful sleep, even as they lay on microscope beds with tiny fiberoptic wires threaded into their brains.
“It was really hard to get the mice to sleep naturally,” said Nedergaard, who spent weeks cuddling the animals in her hands, so they’d learn to feel safe. “But then we said, ‘we really want to not have them disturbed.’”
The reason for this care? Nedergaard studies the glymphatic system, which removes waste from the brain during sleep, so ensuring her test subjects achieve a restorative snooze is central to her work.
In a Cell paper last year, the University of Rochester researcher and her team illuminated the mechanism responsible for this cleaning — work for which they have been awarded the 2026 STAT Madness Editors’ Pick.
More than a decade after Nedergaard’s discovery of the glymphatic system highlighted the importance of sleep for brain health, she now has shown that tightly synchronized oscillations of norepinephrine, blood volume, and cerebrospinal fluid work together to flush out dangerous proteins and toxins during deep, non-REM sleep. The disruption of this process as we age is thought to contribute to the build-up of malformed proteins and the development of neurodegenerative conditions like Alzheimer’s.
Nedergaard and her colleagues also found that some sleep medications can disrupt these natural brain rhythms in mice, potentially impairing the glymphatic cleaning process.
Nedergaard’s research was selected by editors for its innovation, rigor, and potential impact from among 64 teams that competed in the month-long, bracket-style STAT Madness tournament and celebration of biomedical research. STAT readers also crowned a popular vote champion: a team from the University of Michigan Frankel Cardiovascular Center that uncovered a driving force behind abdominal aortic aneurysms.
In an interview with STAT, Nedergaard, who is also affiliated with the University of Copenhagen, explained some of the exciting implications of her research, including its possible application for better tools to screen for — and combat — neurological conditions like Alzheimer’s.
This conversation has been edited for length and clarity.
To start, I’d love to know what brought you to the subject of how the brain clears itself?
It is really that the diseases of aging are basically all about dirty brains. And to me, it makes sense that [the process of clearing the brain] is not a fine molecular pathway. It’s something similar to our garbage removal system, where we just want to dump all the proteins and get them removed.
That is why you can have Parkinson’s, Alzheimer’s, Huntington’s and all these diseases that cause different symptoms and affect different brain regions. But basically they’re all [caused by] protein accumulation that the brain’s immune cells just hate and they start to fight what they see as dirt or foreign objects. And then they make an unhealthy, inflamed environment that gives rise to neuronal death, and that’s why we get dementia.
That was my very simplistic way of looking at neurodegeneration. So that’s what inspired me to this work.
In your paper, you wrote that sleep aids like Ambien affect the way the glymphatic system works, so that even if you’re getting to sleep, you’re not getting the kind of brain clearing that you are with a more natural sleep.
Yeah, that is because of the pump of the glymphatic system. So you can imagine, you have all these donut-shaped tunnels around the blood vessels, and they’re called the pure vascular spaces, and this the [brain’s] plumbing, so, it’s where the cerebral spinal fluid is coming into the brain.
The glial cells have no smooth muscle cells. So instead, they hijack the power of the blood vessels, because they can constrict and dilate. And the way it drives clearing is that when we go to sleep, these blood vessels start to pump. They basically constrict and dilate, and that is pushing fluid outside them in this donut shaped zone. So that’s a major driver. And what the sleep aid does is that it inhibits that pump from working. So you’re still asleep, but the pump is not working.
Does this process happen only when we’re sleeping?
When we’re awake, there’s no time for housekeeping. We have to focus on being awake and evaluating all the things a brain has to do, evaluate the surrounding processes, information, moving us around. It’s like one of my postdocs said, you cannot both prepare for a party and entertain your guests. You have to separate the functions.
You are just back from a conference where you were discussing some of the implications of your research and how it could be applied.
Yeah, it was phenomenal. So, 250 people came, and 92 were on the waiting list, and we had three days of progress. There was a similar conference two years ago, but especially the human imaging has taken off tremendously since then. So basically all the principles of brain fluid flow that were first shown in mice and rats and pigs later, have been shown in human brains now, that you have these donut-shaped tunnels where fluid is going that is more active when you sleep, and so on.
There are, of course, also critiques. People were always skeptical, and there should be that. But basically, the glymphatic has been implicated in almost any neurological disease you can talk about.
And when you think about the possibilities for diagnosis, would you see a possibility for using the glymphatic system to diagnose something like Alzheimer’s earlier?
Yea definitely. So, the neuroradiologist or neuroimager, they’re using all kinds of new sequences on the MRI to try to develop so you can get a glymphogram. And that will probably be routine soon, because there’s so many aspects of it out now. It’s not available yet, of course.
And a glymphogram could be used, in theory, to identify brains that are not clearing themselves right earlier, before someone shows signs of neurological problems?
Yes, it could be. So the hope is that you can actually pick up subjects that are at higher risk for dementia. And maybe by really emphasizing that, you can make lifestyle changes to help [slow or prevent the disease].
Also, a lot of people are looking at medical devices using, I think it’s still only in animals, but they’re using ultrasound and vibration to increase brain clearance. So every day, there are new papers coming out on it.
What surprised you most about the research?
That nobody had described it before! When we saw what was happening, and it was so robust every time, we thought, “Wow, why hasn’t this been described before?” And of course, the foremost reason is nobody could image into the brain before, until photon microscopy became available.
But second of all, people didn’t expect it, because I think neuroscience really teaches that the brain is like a supercomputer, and housekeeping is not that fancy. So I think brain research has focused maybe too much on the higher-level of processing of information and so on, and less on the basic housekeeping.
