Guided by previous research of spider brains, the scientists uncovered evidence of a “waste canal system” in the human brain that internalizes waste from healthy neurons. They discovered that this system can undergo catastrophic swelling, which leads to the degeneration of brain tissue, a hallmark of Alzheimer’s disease.

With over 50 million affected people worldwide, Alzheimer’s disease is among the leading causes of death in the U.S.

The findings, which have been published by The Journal of Comparative Neurology, offer a compelling new explanation for commonly described brain pathologies observed in Alzheimer’s disease, including amyloid-beta plaques, tau tangles, and spongiform abnormalities.

Supported by the Vermont Biomedical Research Network (VBRN), the research was carried out in collaboration among Dr. Ruth Fabian-Fine (Saint Michael’s College, UVM Robert Larner, M.D. College of Medicine), Dr. John DeWitt (UVM Robert Larner, M.D. College of Medicine, UVM Medical Center), Dr. Adam Weaver (Saint Michael’s College), and Saint Michael’s undergraduate research students Abigail Roman and Melanie Winters, both members of the Class of 2025.

“The Vermont Biomedical Network has been thrilled to support Dr. Fabian-Fine’s research from its initial focus on animal neuroscience to the more recent and potentially groundbreaking emphasis on the cellular basis of human neurodegeneration,” said UVM’s Dr. Christopher Francklyn, the Director of VBRN. “Her exciting work, and the outstanding training she has provided to her undergraduate co-investigators, epitomizes what NIH hopes to accomplish with its national IDEA program.”

Neuroscientist Dr. Fabian-Fine and her team initially investigated the underlying causes for neurodegeneration in Central American wandering spiders that suffer from conditions similar to degenerative diseases in humans. Because the spider neurons were a larger size, the scientists were better able to observe their brain functions. They quickly discovered a waste-internalizing glial canal system that undergoes structural abnormalities in degenerating spider brains, which leads to uncontrolled depletion and death of brain cells.

This discovery prompted Fabian-Fine, a Vermont Center for Cardiovascular and Brain Health Pipeline Investigator, to explore whether a similar system could be found in both rodent and human brain tissue, so she teamed up with neuropathologist Dr. DeWitt at UVM’s Larner College of Medicine. The collaborative undertaking led the scientists to gather overwhelming evidence that neurodegeneration in human and rodent brains may have similar underlying causes compared to those observed in spider brains. The scientists’ report outlines possible underlying causes for neurodegeneration that may offer a promising new avenue for drug development that can address the structural abnormalities that lead to neurodegeneration.

Dozens of student researchers at Saint Michael’s College contributed to the multi-year research that provided the foundation for this breakthrough. Experiments occurred at Saint Michael’s College, the University of Vermont Medical Center, and at the UVM’s Center for Biomedical Shared Resources.