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There are about 170 billion cells in the brain, and as they go about their normal tasks, they produce waste—lots of it. In order to stay healthy, the brain needs to flush out all this debris. But how exactly this happens remains a mystery.

Now, two teams of scientists have published three papers that offer a detailed description of the brain’s garbage disposal system. Their insights could help researchers understand, treat and perhaps prevent a wide range of brain disorders.

The papers, all published in the journal Nature, suggest that during sleep, slow electrical waves push the fluid around the cells from deep in the brain to its surface. There, an advanced interface allows the waste products in this fluid to be absorbed into the bloodstream, which takes them to the liver and kidneys to be removed from the body.

One of the exported waste products is amyloid, the substance that forms sticky plaques in the brains of Alzheimer’s patients.

There is growing evidence that in Alzheimer’s disease, the brain’s waste-removal system is impaired, said Jeffrey Iliff, who studies neurodegenerative diseases at the University of Washington but was not part of the new studies.

The new findings should help researchers figure out exactly where the problem is and perhaps fix it, Iliff says.

“If we restore drainage, can we prevent the development of Alzheimer’s disease?” he asks.

A brief history of brainwashing

The new studies come more than a decade after Ilif and Dr. Maiken Nedergaard, a Danish scientist, first proposed that the clear fluids in and around the brain are part of a system for washing away waste products.

Scientists have named it the glymphatic system, a nod to the body’s lymphatic system, which helps fight infection, maintain fluid levels, and filter out waste products and abnormal cells.

Both systems work like plumbing in a house, says Jonathan Kipnis of Washington University in St. Louis, author of two of the new papers.

“You have the water and sewer pipes,” Kipnis says. “So the water comes in clean, then you wash your hands and the dirty water comes out.”

But the lymphatic system uses a network of thin tubes that transport waste to the blood. The brain lacks these tubes.

So scientists have spent decades trying to answer a fundamental question, Kipnis says: “How does a waste molecule from the middle of the brain get all the way to the brain’s borders” and eventually out of the body?

Part of the answer came in 2012 and 2013, when Iliff and Nedergaard began proposing the glymphatic system. They showed that in sleeping animals, cerebrospinal fluid begins to flow rapidly through the brain, flushing out waste.

But what was pushing the liquid? And how was waste transported across the barrier that normally separates brain tissue from the bloodstream?

Waves that wash

Kipnis and his team began looking at what the brain does while it sleeps. As part of that effort, they measured the strength of a slow electrical wave that occurs during deep sleep in animals.

And they realized something: “By measuring the wave, we’re also measuring the flow of interstitial fluid,” the fluid found in the spaces around cells, Kipnis says.

The waves turned out to act as a signal, synchronizing the activity of neurons and transforming them into tiny pumps that push fluid to the surface of the brain, the team reported in February in the journal Nature.

In a second article published in the same issue of NatureA team led by MIT scientists has provided more evidence that slow electrical waves help clear waste.

The team used mice that developed a form of Alzheimer’s. They exposed these mice to bursts of sound and light that occurred 40 times per second.

The stimulation evokes brain waves in the animals that occur at the same, slow frequency.

Tests show that the waves increase the flow of clear cerebrospinal fluid into the brain and the flow of dirty fluid out of the brain. They also showed that the fluid carried amyloid, the substance that builds up in the brains of Alzheimer’s patients.

In a paper published a few weeks earlier, Kipnis showed how debris, including amyloid, appears to pass through the protective membrane that normally insulates the brain.

Kipnis and his team focused on a vein that runs through this membrane.

“You have a sleeve around the vein that’s never completely sealed,” he says. “That’s where it is [cerebrospinal fluid] out’ and transfers the waste to the body’s lymphatic system.

From mice to humans

Together, the new studies suggest that keeping the brain’s waste-clearing system functioning requires two separate steps: one to push waste into the cerebrospinal fluid that surrounds the brain, and another to move it into the lymphatic system and eventually out of the body.

“We described them separately,” Iliff says, “but biologically they are almost certainly related.”

Iliff says many of the new findings in mice still need to be confirmed in humans.

“The anatomical differences between a rodent and a human,” he says, “are quite substantial.”

But he says the results are consistent with research into what leads to neurodegenerative disorders like Alzheimer’s.

Researchers know that the brain’s waste-clearing system can be disrupted by age, injuries and diseases that clog blood vessels in the brain.

“These are all risk factors for Alzheimer’s disease,” Iliff says.

Impaired waste removal can also be a factor in Parkinson’s disease, headaches and even depression, Iliff says. So finding ways to help the brain clear itself—perhaps by inducing these slow electrical waves—could prevent a wide range of disorders.