Working Towards a Cure: Investigating Neurodegeneration in Alzheimer’s Models

Journalist: Josie Brett | Editor: Anjali Boyd | Photographer & Videographer: Diego Serrano

To most people, a worm is just a worm. But for Victor Stolzenbach, ’18, worms serve as the model organisms for his Alzheimer’s disease research. He is currently working with microscopic nematodes, Caenorhabditis elegans, for his senior thesis on the effects of synthetic compounds on beta amyloid induced neurodegeneration.

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His research focuses on beta amyloid, a kind of hard-to-remove “plaque” protein that builds up in the brain and is thought to be the cause of the onset of Alzheimer’s disease.

“Plaque can build up on your teeth [and] you can brush it out,” said Stolzenbach.“But unfortunately, the brain has no way to do that.”

Over time, the plaque build up can become toxic, and eventually it can cause neuron die-off. To investigate this further, Stolzenbach and his team tested different organic compounds that could allow the worms to clear the plaque in a non-toxic way that would prevent both further neuron degeneration and the decreased lifespan traditionally associated with Alzheimer’s disease.

So far, their research has been successful. The drug they have been testing has had a positive effect on the worms. Inside the worm’s neurons, beta amyloid can build up and cause an early death, but they’ve found that after administering their drug, the worms are living longer. This extended lifespan is an indicator of a beta a drug’s presence in the worms is quite visible due to the fluorescent glow of the neurons where the drug is active.

“If you look at one of these worms when they’re very young, you see all these beautiful glowing neurons.” said Stolzenbach. “A couple days later, you’ll look at the same worm, and you’ll see a lot of degeneration.”

The telltale sign that the drug is working are the presence of these fluorescing neurons after multiple days; when the worms still have five glowing neurons in their tails, it is a clear indication of their drug at work.

“We found that when we administer the drug … more of them have five neurons in their tail after seven days, which is about the average lifespan.”

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Publication is definitely in the future for this research, according to Stolzenbach. He recently presented a poster about his research at the 11th Annual Eckerd College Student Research Symposium. At the event, Stolzenbach interacted with current Eckerd students, faculty members, symposium judges, visiting scientists, and members of the public, and the familiar setting served as a great step toward the future publication and presentations.

“Before we do [publish] we just want to iron out all the kinks and make sure we have everything down.”

He believes that this research experience has benefitted him in more ways than one. Originally a Marine Science major, Stolzenbach became interested in cellular biology during his sophomore year when he took the Cellular Processes class. In his junior year, he took a course with Dr. Denise Flaherty, an Assistant Professor of Biology at Eckerd College, which eventually lead to an independent study and a summer research project in cellular biology and pathways.

“When I first came into this, I had a very light knowledge of how to make your own experiments [and] how to test your own theories,” he explained. During the summer Stolzenbach spent working with Dr. Flaherty, he learned how to design and set up an experiment, as well as how to troubleshoot problems with regards to his research.

As for the significance of the research, Stolzenbach hopes that eventually it will become beneficial to people suffering from Alzheimer’s. The next step may very well be a larger mammal, and one day, there may even be a human trial. However, he is also aware of the possibility of inconclusive results, but Stolzenbach is hardly deterred by this potential outcome.

“Even if we find that halfway through the mouse trials that it’s not having the effects we wanted, it’s still very beneficial,” said Stolzenbach. “It tells other people we’ve already looked here at this type of compound, and it’s been shown not to do anything,”

Stolzenbach’s calm response exemplifies his firm grasp on the many layers of the scientific process. He understands that either result will serve as a benefit for the future of the research.

“It saves somebody the extra time down the road. You never know, 20, 30 years from now somebody’s looking at the same kind of compounds we are … and say ‘maybe it didn’t work, but they went on to a better project.’”

Stolzenbach’s plans upon graduation are to return home and work as a laboratory technician for a year or two before applying to graduate school. Though he has not yet made a decision of where he would like to pursue graduate work, he hopes to further his studies somewhere warm, possibly in California or Florida. For now, though, Stolzenbach is grateful for the knowledge and experience he has gained to prepare him for the next steps of his career.

“It’s like you have another piece of the puzzle,” he said. “We know a little bit about what [the drug] does, we know where it goes … and we don’t have to spend any more time on it and [can] move on to other obstacles.”