Alzheimer's disease makes worms unable to move. Professor Jessica Tanis's laboratory at the University of Delaware helped the worms with Alzheimer's disease to keep their wiggle.
Tanis and her team solved the mystery to reveal new clues about the possible impact of diet on Alzheimer’s, the debilitating brain disease that affects more than 6,000,000 Americans.
Tanis and her colleagues began to investigate factors that could influence the progression and onset of Alzheimer's disease a few years back. They were working with C.elegans, a small soil-dwelling worm. This prompted a number of studies.
Within 36 hours of reaching adulthood, the worms are paralysed by amyloid beta, which is a toxic protein that can be linked to Alzheimer's disease. Tanis's lab made the worms immobile in one petri dish, but scientists documented the "body bends" of the worms in another petri dish.
Tanis, an assistant professor at UD's Department of Biological Sciences, said that "it was an observation my master student Kirsten Kervin made." "She repeated the experiment repeatedly with the same results."
Tanis stated that the team discovered a crucial difference after years of research. All the worms were fed E.coli. However, one strain had higher levels than the other. Tanis originally focused her research on genetic factors, but she decided to refocus her efforts to study this vitamin and its protective function.
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Learn from the worms
C. elegans, also known as a nematode is a small, translucent worm that lives in soil and eats bacteria. This worm has been studied extensively since the 1970s as a model organism. It is simpler than humans and can be used to study cell biology and disease.
Tanis stated, "As humans we have a lot of genetic diversity and so complex diets it is difficult to determine how one dietary factor affects the onset or progression of Alzheimer's." That's why worms are so amazing. We use worms with the exact same genetic background. They react to amyloid beta just like humans. And we can precisely control what they eat so that we can get to the molecular mechanisms.
The brains of people with Alzheimer's have toxic effects from amyloid beta buildup over time. This causes reduced energy, fragmentation in the mitochondria, which are the cells' power sources, and oxidative stress due to an excess of free radicals. Tanis stated that the same thing occurs in C. elegans in just a few hours. Paralysis occurs in the worms when Amyloid beta is present.
Tanis stated, "The readout is black or clear -- the worms either are moving or not." "When we gave vitamin B12 (to the worms deficient in vitamin B12), paralysis happened much slower, which indicated that B12 was beneficial. The worms that had B12 had lower energy levels and oxidative stress.
The team discovered that vitamin B12 is dependent on methionine synthase for its effectiveness. Tanis stated that B12 is ineffective without the presence of this enzyme. The vitamin can only be added to the diet if animals are deficient in it. Animals with normal levels of B12 do not benefit from more B12. Researchers also found that vitamin B12 did not affect amyloid beta levels of the worms.
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Team power Tanis
Tanis is grateful for the hard work and contributions of her students. Andy Lam, the first author of the research article is pursuing a dual degree in biology and business administration at UD. He worked for years on the critical laboratory protocols. He conducted dozens to dozens of experiments, and documented the observations over night many times.
Future goals include automating these experiments with a high-throughput system from UD's Bio-Imaging Center and deep learning analysis to detect if worms move or not. This would enable the team to examine more quickly the interplay between diet and genetics.
Tanis stated, "We have essentially identified the molecular pathway" and that they are now looking for other activations. "Can B12 protect multiple neurodegenerative diseases like ALS and Parkinson's?" We're looking into it."
Kirsten Kervin, a graduate of UD with a master's degree, is now a researcher scientist at WuXi AppTec Philadelphia. However, it was her keen observation about C. elegans which set the project in motion.
Tanis stated, "That first observation opened up an entire new world. Which is somehow the story for my research career at UD." I thought I would be studying one subject, but I now am studying another. It hasn't always been easy, but it has led to a whole new area of research that we are now pursuing.
The "we" that is working on this project now include two graduate students, a postdoctoral researcher associate, and three undergraduate students. There are also collaborations with the BioImaging Center and several UD labs.
Tanis stated that there is currently no treatment for Alzheimer's. There are some things you can't change. You cannot alter the fact that you have Alzheimer's and your genetic predisposition. What you eat is one thing that you can control. It would be amazing if people could alter their diets to prevent the onset or progression of diseases. This is something that my lab is eager to continue exploring."
This work was funded by grants from the University of Delaware Research Foundation, the NIH-funded Delaware INBRE Program, where Tanis was a pilot researcher, and an NIH Alzheimer's Supplement grant.
