The human brain is composed of about 170 billion cells, which produce a significant amount of waste during their regular functions. For the brain to remain healthy, it needs to efficiently clear away this debris, but the mechanism behind this process has been largely unknown. Recently, two teams of scientists have published three papers in the journal Nature, shedding light on the brain’s waste-removal system. These insights could pave the way for better understanding, treatment, and prevention of various brain disorders.
The studies suggest that during sleep, slow electrical waves push fluid from deep within the brain to its surface. At this surface, a complex interface allows waste products in the fluid to be absorbed into the bloodstream, which then carries them to the liver and kidneys for removal from the body. One notable waste product is amyloid, the substance that forms plaques in the brains of Alzheimer’s disease patients.
Jeffrey Iliff, a neurodegenerative disease researcher at the University of Washington, who was not involved in the new studies, comments on the growing evidence that Alzheimer’s disease impairs the brain’s waste-removal system. The new findings could help identify where this problem occurs and how it might be rectified. Iliff asks, “If we restore drainage, can we prevent the development of Alzheimer’s disease?”
The exploration of the brain’s waste-clearance system began over a decade ago when Iliff and Dr. Maiken Nedergaard, a Danish scientist, proposed that the clear fluids in and around the brain are part of a system designed to wash away waste products. They named it the glymphatic system, paralleling the body’s lymphatic system, which fights infection, maintains fluid levels, and filters out waste and abnormal cells. Jonathan Kipnis of Washington University in St. Louis, an author of two of the new papers, explains that both systems work like plumbing in a house. “You have the water pipes and the sewage pipes,” he says. “So the water comes in clean, and then you wash your hands, and the dirty water goes out.”
However, unlike the lymphatic system, which uses a network of tubes to transport waste to the bloodstream, the brain lacks these tubes. This led scientists to investigate how waste from the middle of the brain makes its way to the borders of the brain and ultimately out of the body. Part of the answer came in 2012 and 2013 when Iliff and Nedergaard proposed the glymphatic system, demonstrating that cerebrospinal fluid flows through the brain during sleep, flushing out waste.
The recent studies aimed to understand what propels this fluid and how it crosses the barrier between brain tissue and the bloodstream. Kipnis and his team examined the brain’s activity during sleep and measured the power of slow electrical waves that occur during deep sleep. They discovered that these waves act as signals, synchronizing neuron activity and turning them into tiny pumps that push fluid toward the brain’s surface. The team reported in Nature that this mechanism helps transport waste.
In another study published in Nature, researchers at the Massachusetts Institute of Technology found more evidence supporting the role of slow electrical waves in waste clearance. They used mice genetically engineered to develop Alzheimer’s-like symptoms and exposed them to bursts of sound and light at 40 times per second. This stimulation induced brain waves that increased the flow of clean cerebrospinal fluid into the brain and the flow of dirty fluid out, carrying amyloid.
Kipnis’s team also explored how waste crosses the protective membrane that usually isolates the brain. They focused on a vein passing through this membrane, finding that cerebrospinal fluid transfers waste to the body’s lymphatic system through a partially sealed sleeve around the vein.
These findings indicate that maintaining the brain’s waste-clearance system involves two steps: pushing waste into the cerebrospinal fluid and then moving it into the lymphatic system for removal from the body. Iliff emphasizes that although described separately, these processes are likely interconnected biologically.
While these discoveries were made in mice, they align with what researchers know about neurodegenerative disorders like Alzheimer’s. Iliff points out that the anatomical differences between rodents and humans are substantial, so the findings need to be confirmed in people. However, the results are consistent with research on factors contributing to such disorders. Researchers have identified that age, injuries, and diseases that clog brain blood vessels can impair the brain’s waste-clearance system, all of which are risk factors for Alzheimer’s disease.
Iliff also suggests that impaired waste removal might contribute to Parkinson’s disease, headaches, and even depression. Thus, inducing slow electrical waves to aid brain self-cleaning could potentially prevent a wide range of disorders.
