What Can Spiders Tell Us About Alzheimer’s Disease?

Scientists use many small and strange organisms — like fruit flies, zebrafish, and see-through worms — to understand the inner workings of the brain.  

Ruth Fabian-Fine has spent her career studying the brain by looking at one such model organism, the Central American wandering spider. They’re ideal for looking at the brain because their brain cells are very large relative to their body, which makes it easier to study them. 

When she started up her lab at St. Michael’s College, something strange started happening to the spiders — they couldn’t crawl up on walls or hunt prey efficiently. “They all showed neurodegeneration at young ages,” she told Being Patient. “I decided to look into the reason why their nervous system degenerates.” 

Fabian-Fine discovered a waste clearance pathway in the brain that went haywire in the spiders and may contribute to Alzheimer’s disease in humans. The findings were published in the Journal of Comparative Neurology last year.

What happened to the spiders?

Fabian-Fine and her colleagues dissected the spider’s brains and used microscopes to look for clues. The supportive cells of the brain, the astrocytes — which are involved in waste clearance, signaling, and mounting an immune response — had sprouted canals that connected to neurons. 

While these strange structures weren’t previously characterized by other scientists, they were familiar to Fabian-Fine, who first spotted the canals in graduate school.

She believes they work like vacuums. A protein called aquaporin-4 lined their walls, which allowed liquid waste from neurons to be sucked up by the astrocytes. In the spiders that developed neurodegeneration, the tunnels were bloated and overflowing with waste. 

Fabian-Fine hypothesized that the canals were sucking up too much, depleting the cells of their contents, causing them to degenerate and die. 

What caused these tunnels to fail in the first place? The protein machinery that held the canals together was temperature-sensitive. Too cold, and they can’t work properly. “The window that the spiders were on had a draft in the wintertime,” said Fabian-Fine. “That’s why these canals unraveled and brought these neurons to neurodegeneration.”

Do humans also have this waste clearance system?

Many important discoveries that impact human health start off as curious observations in other organisms.

“By studying the nervous systems of other organisms, we gain valuable insights into potential functions of our own cells that can ultimately lead to a much better understanding of disease,” Melissa Cooper, a scientist at NYU Langone who wasn’t involved in the research, told Being Patient. 

Working with a neuropathologist, Fabian-Fine spotted cells with nearly identical features in the memory region of the brain, called the hippocampus, in postmortem brains. 

These astrocyte cells, called ependymal glia, were found near the brain’s ventricles. That’s significant: Ventricles are cavities within the brain that carry cerebrospinal fluid and may help the brain eliminate waste. Fabian-Fine thinks these canals might be trafficking waste out of the brain through the ventricles in healthy people. 

But in the brains of people who died with Alzheimer’s disease, these canals also looked swollen. The nearby neurons were “empty”, almost as if the canals had sucked out all their contents. The researchers also found the hallmark proteins of Alzheimer’s disease, beta-amyloid and tau, near these canals too. 

Cooper said the study “could have broader implications on our understanding of the clearance of problematic proteins, such as amyloid.” The connection between the brain’s waste clearance pathways and brain health has been a hot topic of debate among neuroscientists — some believe it to be a missing piece of the Alzheimer’s puzzle while others question its role.  

Fabian-Fine also thinks that microbes might cause trouble for these canals, potentially sparking Alzheimer’s. In the last few years, more evidence emerged linking Shingles, Herpes, and other infections to Alzheimer’s, as well as some evidence that preventing or treating infections could reduce risk.

“Alzheimer’s patients have a very high incidence of fungal, bacterial and viral infections,” said Fabian-Fine. “If you have a canal system, you need to break down this debris, because if you don’t break it down, there’s the danger of blocking this canal system.” 

Her research group is now looking at a fungal protein called chitin to see if it’s messing with the vacuum.

The research was supported in part by an NIH grant (P20GM103449).