A new study published in the Journal of Comparative Neurology has identified a previously unknown waste-clearing system in the human brain that appears to play a key role in maintaining healthy neurons. The researchers found that specialized glial cells use tiny canals to draw waste from neurons into structures that resemble microscopic receptacles. When this system becomes structurally impaired, the result may be catastrophic swelling and neuronal decay—hallmarks of Alzheimer’s disease. The team made the discovery by first studying a similar system in spider brains.
Alzheimer’s disease is the most common form of dementia, affecting millions of people worldwide. It is characterized by progressive memory loss, confusion, and changes in thinking or behavior. Scientists have long associated these symptoms with two types of protein buildup in the brain: amyloid beta plaques and tau tangles. But how this waste forms and accumulates—and whether it causes the disease or results from it—remains unclear. One hypothesis is that problems with waste removal mechanisms may be involved.
The new study was led by neuroscientist Ruth Fabian-Fine at Saint Michael’s College, who had been studying brain degeneration in the Central American wandering spider. Some of the spiders in her lab began showing early signs of neurodegeneration, prompting her to investigate their brain structure more closely. What she found was unexpected: a network of glial cells forming myelin-wrapped “canals” that extended into neurons to remove cellular debris. These canals appeared to be a built-in cleaning system for the brain. When they failed, the spiders’ neurons hollowed out and died.
“This discovery was really by accident. We are working with an invertebrate model system using the Central American wandering spider, Cupiennius salei. When I relocated to the United States, many of the animals showed behavioral signs of neurodegeneration at young ages, when they should not have these symptoms,” explained Fabian-Fine, an associate professor of biology and neuroscience.
“To rescue the colony, we investigated why the nervous system degenerated in these animals. I realized that the problem was the structural abnormality of a canal system that I had initially discovered during my Ph.D. work in Germany. My research showed that the affected system is a glial canal system that removes waste from spider neurons. As this system failed structurally in degenerating spiders, the result was that it catastrophically depleted neurons of their content.”
“I further discovered that the reason why it failed in the United States and not in my labs in Germany or Canada was that the temperature in the spider room was lower. This caused important enzymes that maintain critical structural proteins in this system to slow down, which led to the neurodegeneration.”
Realizing the potential significance of this system, Fabian-Fine collaborated with neuropathologist John C. DeWitt at the University of Vermont. Together, they examined brain tissue from rats and humans—both healthy individuals and people who had died with Alzheimer’s disease. Using advanced imaging techniques, including electron microscopy and RNA labeling, they discovered a nearly identical glial canal system in human hippocampal tissue. These canals were formed by ependymal glial cells, which express the water channel protein aquaporin-4 and extend long myelinated projections into nearby neurons.
In healthy human brains, these projections appeared to remove cellular waste efficiently by forming small waste-receptacle structures inside neurons. But in tissue from Alzheimer’s patients, the system appeared to break down. The glial cells became swollen and malformed, and their projections expanded into large, bulbous structures packed with cellular debris. This swelling was often accompanied by the gradual loss of cytoplasm in neurons, eventually leaving them empty and dead. The researchers proposed a new term for this process: “gliaptosis,” a form of glial-induced neuronal death.
The team also found that these waste-receptacle structures were marked by proteins linked to Alzheimer’s, including amyloid beta, tau, and presenilin 1. In early stages of degeneration, these proteins appeared to accumulate in small glial protrusions that had invaded neurons. In advanced stages, these waste-filled structures expanded and overwhelmed the neurons’ interiors, aligning closely with the spongy, hollow appearance often seen in Alzheimer’s-affected brain tissue.
Notably, the researchers saw the same patterns in spider neurons. In healthy spiders, the glial canal system appeared intact and functional, with clear structures for waste removal. In older or degenerating spiders, the canals became disorganized and expanded, leading to neuronal collapse. Because spider neurons are larger and easier to study than human ones, the researchers were able to observe these changes in much greater detail.
The study raises questions about the traditional understanding of brain myelination. Myelin is typically thought of as a substance that insulates axons to help them transmit electrical signals. But the findings suggest that some myelinated glial cells may instead serve a different function: waste removal.
In both spiders and mammals, these glial cells formed long, thin canals that penetrated neurons and drew out waste. This process appeared to depend on aquaporin-4, a protein that facilitates water movement across cell membranes. The authors propose that a water-driven “bulk flow” helps move debris from neurons into the glial cells, where it can then be disposed of through drainage canals.
One striking implication of the study is that this brain-cleaning system may be evolutionarily ancient. The fact that spiders and humans share such a similar mechanism suggests that it has been preserved across hundreds of millions of years. This could point to its importance in maintaining healthy brain function across species. But it may also indicate a shared vulnerability: if this system breaks down, the result could be neurodegeneration.
“Since this publication, we have conducted significant research. We have another paper under review that shows what amyloid-beta plaques really are—that they are not randomly misfolded protein aggregates but waste-internalizing receptacles in a failing waste removal system. All of our findings confirm what we propose,” Fabian-Fine told PsyPost.
“Particularly in light of all the uncovered fraud in Alzheimer’s research over the past decades, I would like for the general public to know that—knowing what I know—I am extremely optimistic that we are on the right track and that we will be able to address neurodegeneration clinically in the near future. It is a question of funding and acceptance, and I am working on both. Once you see the structures I show in my papers, you cannot unsee them, and this is why I am hopeful that this will be accepted soon.”
The researchers caution that while their findings are compelling, more research is needed to confirm the exact mechanisms involved. For instance, it remains unclear whether the observed glial swelling is a cause or a consequence of waste buildup. It’s also not yet known whether boosting the function of these glial canals could help prevent or slow the progression of diseases like Alzheimer’s. Future studies will need to explore these questions, ideally by examining the system in living brain tissue or animal models.
Fabian-Fine and her colleagues plan to continue investigating the structural and molecular features of this glial canal system. Their goal is to better understand the proteins and processes involved so they can identify what goes wrong during disease and how it might be prevented. They hope that by mapping out this ancient and overlooked system, they can open up new pathways for treating Alzheimer’s and other forms of dementia.
“Neurodegeneration is likely irreversible, which is why I am working around the clock to drive this research forward and get acceptance and clinical trials on the way,” Fabian-Fine explained. “But even if the drug targets I have identified are effective in clinical trials, it will not reverse the damage that has been done in affected patients. It will likely slow or halt progression. This is why time is of the essence—so that we can achieve early and preventative treatment before damage has been done.”
“We are working on describing this entire system and important proteins and structures in this system. We need this information to understand what goes wrong in disease and how to prevent this. I would like for readers and scientists to be open to this discovery. Figure 10 in our latest paper shows that once you put the glial canal system (tanycytes) in place you can explain the clinical manifestations of an Alzheimer’s-affected brain. Why would we not explore this?”
The study, “Myelinated Glial Cells: Their Proposed Role in Waste Clearance and Neurodegeneration in Arachnid and Human Brain,” was authored by Ruth Fabian-Fine, Adam L. Weaver, Abigail G. Roman, Melanie J. Winters, and John C. DeWitt.
