How does the brain clear ‘waste’ to protect itself?

• Alzheimer’s disease currently affects about 32 million people globally and has no cure.
• One of the leading theories behind Alzheimer’s disease is the accumulation of the proteins beta-amyloid and tau in the brain.
• Researchers from Oregon Health and Science University show for the first time how the brain’s glymphatic system removes ‘waste’ that could cause problems further down the line.
• Scientists believe this finding emphasizes the importance of quality sleep to keep the brain’s waste-removal system running properly.
• It remains unclear to what extent these findings may have implications for Alzheimer’s disease and other forms of dementia.

One of the leading theories behind Alzheimer’s disease is that the toxic accumulation of the proteins beta-amyloid and tau in the brain can cause many of the symptoms related to this condition.

“Alzheimer’s and several other progressive brain diseases — such as Parkinson’s disease — are caused by the abnormal accumulation of proteins in the brain,” Juan Piantino, MD, associate professor of pediatrics in the Division of Neurology in the School of Medicine and faculty member of the Neuroscience Section of the Papé Family Pediatric Research Institute at Oregon Health and Science University told Medical News Today.

“Removing those proteins is essential to brain health, but the process is poorly understood. If we can improve our brain’s ability to remove such proteins, we might be able to alter the course of those diseases,” he suggested.

Piantino is the senior author of a new study that for the first time shows how the brain’s glymphatic system clears away these proteins, emphasizing the importance of lifestyle measures such as enough quality sleep to keep the waste-clearing system efficiently working.

For this study, Piantino and his team recruited five participants who underwent neurosurgery to remove tumors in their brains. All participants consented to having a gadolinium-based inert contrasting agent injected into their cerebrospinal fluid during the operation, which would then travel to the brain.

Study participants then underwent a special type of magnetic resonance imaging (MRI) called fluid attenuated inversion recovery (FLAIR) at 12, 24, or 48 hours after surgery to see how the contrasting agent spread into the brain.

“Often, patients receive a contrast agent — a type of substance that can be seen on MRI — via an IV or, in our case, a spinal tap,” Piantino explained. “FLAIR allows us to see where that contrast goes with great detail.”

At the study’s conclusion, researchers definitively showed a waste-clearing system in the brain through its network of perivascular spaces, which are areas filled with fluid that surround small blood vessels.

“The brain uses an enormous amount of energy and generates waste, which needs to be removed,” Piantino detailed. “Scientists have shown that in mice, one way the brain removes waste is by ‘flushing’ fluid (essentially water) through its tissue — think of it as a person doing the dishes on a kitchen sink. The brain circulates fluid through specific channels (the perivascular spaces).”

“Although this was an exciting finding, no one has shown that this model was true in humans until now,” he continued.

In this new study, Piantino, said:

“We have shown that in humans, fluid enters these channels and is pushed into the tissue, as observed in mice. This finding is crucial in characterizing how waste is removed from the brain in humans.”

Past research has shown that proper sleep can have a positive impact on the brain’s glymphatic system and its ability to clear out waste. Piantino and his team believe their findings further emphasize the importance of quality sleep to ensure a well-functioning glymphatic system in the brain.

“Going back to the sink analogy, waste removal happens mostly at night during sleep, like we do our dishes at night,” Piantino said. “Improving our sleep might be a crucial way to improve our waste removal. In addition, several drugs that can improve waste removal are currently being studied.”

“We are currently testing ways to enhance waste removal without drugs,” he added. “We want to know how sleep can affect waste removal.”

Piantino encouraged people who would like to volunteer as participants in his and his team’s upcoming studies to get in touch with them at [email protected].

One hope is that further insights into the brain’s “waste-disposal” system could eventually contribute to preventive strategies for Alzheimer’s and other forms of dementia. However, not everyone is fully convinced by this prospect.

After reviewing the current study, Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, no involved in the research, told MNT he was excited to see researchers starting to figure out how to image the brain’s glymphatic system with MRI imaging.

Yes he also said that: “As a neurologist who treats patients with neurological diseases, I do not expect the presence of a central nervous system lymphatic system or glymphatic system to have any clinical significance outside of neuro-oncology and neuro-infectious disease.”

“Lymphatics play a role in the spread of infections and cancer. There is no expectation central nervous system glymphatics can transport proteins inside of the central nervous system as lymphatics outside of the central nervous system cannot do this,” explained Segil.

“This study did not claim central nervous system lymphatics can transport any amyloid or tau proteins,” he cautioned. “This study is going to help neurologists treat central nervous and brain tumors and infections and has no relevance to cognitive behavioral neurology practice.”

As the study participants all had brain tumors surgically removed prior to their MRI imaging, Segil also noted they may have glymphatic systems that are different to healthy people.

“I would like to see the same study performed in patients with central nervous infections and in patients with metastatic brain disease who have cancers in other parts of their bodies which have swum to their brain and eventually in some healthy humans,” he told us.

“Glymphatic imaging in the future I think will help neurologists treat patients with brain tumor and brain infections but is unlikely to help cognitive behavioral neurologists diagnose or treat patients with memory loss or dementias,” Segil opined.