Kate Evans

Using Tau Protein to Investigate the Link between Sleep Deprivation and Alzheimer’s Disease in a Drosophila Model

April 5, 2021   /  

Student Name: Kate Evans
Major(s): Neuroscience
Advisors: Dr. Seth Kelly and Dr. Rebecca Williams. Second Reader: Dr. Erzsébet Regan

Neurodegenerative disorders affect millions of people in the world every year. One widely studied neurodegenerative disorder is Alzheimer’s Disease. Alzheimer’s Disease (AD) can be characterized by tau tangles, which are formed from the hyperphosphorylation of tau protein in a neuron. Many factors can contribute to AD, and previous literature suggests that proper sleep may play an important role in preventing the onset of AD. This study aimed to find a relationship between sleep deprivation by using transgenic Drosophila that were manipulated to carry the human tau protein. The Drosophila were then sleep deprived to search for an increase in tau protein. The tau protein was quantified using western blotting techniques, and activity monitors tracked the movements of Drosophila to investigate the impact of the transgene on the sleeping patterns. The study discovered that flies transgenic for AD slept less. The transgenic Drosophila also showed that they had a larger amount of tau protein, but this was not significantly shown through the data. This study provides a strong basis to further investigate the connection between AD and sleep deprivation in Drosophila and other model organisms. The finding of this study should be considered to help avoid the onset of Alzheimer’s Disease.

Kate will be online to field comments on April 16: 10am-noon EDT (Asia: late evening, PST 6am-8am, Africa/Europe: late afternoon).

55 thoughts on “Using Tau Protein to Investigate the Link between Sleep Deprivation and Alzheimer’s Disease in a Drosophila Model”

  1. Thanks for sharing your project Kate! I’m wondering if you think Tau protein would increase in the WT SD flies. But maybe first I need to know if WT flies would even produce Tau without the transgenic manipulation.

    1. Thank you, Dr. Stav! Unfortunately, the normal WT flies do not contain the gene for hTau-so if we were to run western blot on them, there would be no protein present on the blot. Since it is a human disease, it is a little tricky to study in Drosophila, but inserting the human tau into the fly genome seems to be a good representation of AD.
      If the flies could naturally produce tau, I definitely think that SD could cause an increase in tau, which will lead to speeding up the onset of AD.
      Thanks for your thoughts; I will miss being in your class(es) next year!

  2. Do you believe that the results would be linear across other species, such as rats? Congratulations!!!-WY

    1. Yes! I plan on investigating this if I get the opportunity in the future. With rats, we could also manipulate them to carry AB plaques- another hallmark of Alzheimer’s disease. This could strengthen the results found if both AB plaques and tau protein would increase with the onset of sleep deprivation.
      Thanks for your question Willis!

  3. Congrats on all of your hard work! I enjoyed your presentation very much! I cannot wait to see what the future holds for you and any further research you complete!

      1. I think it would be interesting to know what prompted your interest in studying this subject?

        1. I was first inspired by my grandfather, who suffered from Alzheimer’s disease until his passing. I am hoping my research will help these millions of individuals that are affected with neurodegenerative diseases by implementing preventative measures. If something as simple as proper sleep can help with the avoidance of the disease, I feel like this is very important to investigate!

    1. Congratulations Kate! I’m so proud of all the hard work you’ve put into your research! You’ve worked so hard to come this far and I’m excited to see where you go on your next journey! Keep up the hard work!

  4. Kate!!! Congratulations!!! I watched this with my mom and we were both fascinated by this research. I was wondering, do you think the results would be different in a rodent model?

    1. Ah, I didn’t refresh the page before asking my question and I see that someone else asked that question! Still, congratulations my friend!!!

    2. Thank you both so much for watching! Since Alzheimer’s disease is able to be studied among humans, Drosophila, and rodents, I do think that I could have some similar results. With the rodent model, I would be interested in using behavioral tasks, like mazes and such, to test if the Alzheimer’s disease is present in the rodent before I were to perform the sleep deprivation. Then, I could ensure that the tau protein was present before looking to see if sleep impacted the severity.
      Thank you again for stopping by!

  5. Congratulations Kate!!
    You mention that hyperphosphorylation of tau occurs in disease states. Could you explain why this hyperphosphorylation occurs? Like is due to the hyperactivity of a kinase because of a mutation or could it be caused by something else?

    1. Thank you so much! Yes, hyperphosphorylation of tau can occur, and there are many theories as to why this happens. One prevalent theory right now is the mutation of the protein kinases like you said. Once it is hyperphosphorylated, the diseased tau will actually latch onto the microtubule in place of the healthy tau, and cause the tau tangles, which we know to be a hallmark of AD.
      Thank you so much for stopping by!

  6. Kate,
    Congratulations on your achievement and hard work. The future is up to you and how you want to write your life. You have always put your all into everything you do, excited for you and the great accomplishments you have done and will do.

  7. Kate, Great Job!!!

    This was a nice presentation and provided a great introduction to your project. I also liked the concept map that you used to introduce your objectives.

    You’ve done a very nice job here presenting the results of your study too. Thanks so much for all your hard work this year!

    1. Thank you so much, Dr. Kelly! I really appreciated all of your help in this project- I’m grateful for everything I learned this year!

  8. Hi Kate, great work!!! I have a couple of questions. What made you decide on sleep deprivation for 3 hours per night rather than sleep deprivation through the 12 hour dark cycle? And do you think that longer periods of sleep deprivation would result in a more dramatic increase in Tau?

    1. Thanks for the question, Noah! So I chose to do the 3 hours a night for five days to represent a more chronic sleep deprivation. I could have also done one day of 24 hour sleep deprivation, but I chose to do it across a period of five days because I thought it was more likely for individuals with AD to have trouble sleeping for a few hours a night, rather than just missing a whole night of sleep.
      I think a longer period of sleep deprivation for the flies could result in an increase in tau protein. But I was also concerned of sleep depriving the flies too much, and risking them not being able to survive for the whole experiment.
      However, I think it would be interesting to see the comparison of one day of 24 hours sleep deprivation compared to five days of 3 hours.
      Thank you for checking my project out!

      1. Great idea with trying to capture a more AD-like patient model with small amounts of sleep dep, that makes a lot of sense. That would be my guess too that longer bout of sleep deprivation might lead to increased tau, and I agree that it could be lethal.

        1. Thank you! To be fair, these flies were only 3-7 days old when implemented with SD. My guess would be that they would probably be okay to have longer SD, but if the flies were more aged, then this would most likely have lethal effects.

  9. Loved the presentation. Very proud of you. So are you saying that proper sleeping habits could possibly curb the onset of Alzheimer’s in some people? If so it might already be too late for me.

    1. Thank you so much! My research suggests that this is possible, but further studies are needed to confirm. If my hypothesis holds correct, I think that while implementing proper sleep is important in younger populations as well, it is extremely important in an aging population, 65 years or older. You might be alright for now, but changing your sleeping habits soon couldn’t hurt! 🙂

      1. Thanks for not letting on that I’m old. But I will keep it in mind because I don’t think your mom would be able to handle me being senile.

  10. Congrats on finishing Kate! I really enjoyed working with you in lab and can’t wait to see what you do in the future. Do you plan to continue research in Alzheimer’s Disease moving forward, or do you plan to use this project as a stepping stone to another area?

    1. Thank you, Muira! I enjoyed working alongside you as well! I would love to continue Alzheimer’s disease, and neurodegenerative diseases in general- I really think that this research can impact so many families!

  11. Congratulations Kate!! Your project is quite interesting and intriguing. I wish you all the best in the future.

  12. Congratulations Kate!! I really enjoyed how you presented the information and I learned a lot about Alzheimer’s. In the future, do you think that the older flies would have an increased amount in tau tangles compared to the young flies? It would be really cool to eventually collect enough data to create a pseudo risk chart for Alzheimer’s based on fly age!

    1. Thank you, Grace! That’s a great idea! If I were to be able to repeat this experiment again, I would wait around 21 days before implementing the sleep deprivation to ensure that the tau tangles have formed. Since Alzheimer’s disease is a primarily age dependent disease in humans, my thoughts are that they would stay consistent in flies. I would hypothesize that the longer the flies are aged, the more tau tangles are present. It would be a great idea to increase the age of the flies each round, and then use them for western blots to determine the amount of tau present. Thanks for stopping by!

  13. Hi Kate,

    I’m really proud of your hard work this year! Well done. Your presentation looks awesome!

    I wish you all the best as you move forward in your career. I’m glad we were granted the opportunity to work together. I learned so much from your project!

    Best of luck with your future,
    Dr. Williams

    1. Thank you so much Dr. Williams!
      I am so glad that our paths crossed at Wooster, and I am grateful for all the advice you gave me! I am excited to take this knowledge to my future steps.
      I will miss you next year!

  14. Congratulations Kate! I really enjoyed your presentation and think your research is so interesting, important, and relevant.

  15. Hi Kate,
    Awesome to see the study come together after the whole year, and see your results! Glad I had read “Why We Sleep” my softmore year otherwise I would be horrified after all these (at times quite literally) sleepless nights working on IS. Hope that book was interesting

    It’s always been good to talk with you at the library, good luck with your future research!

    1. Thank you so much Justin! “Why We Sleep” was definitely a great book for background of this experiment. It was always nice talking to you at work. I know you’ll do great wherever you end up!

  16. Congratulations on completing this awesome research, Kate! I’m amazed by the connections that can be drawn between our studies.. for example, my mice were tested at an early age, as well, despite AD being an age-related disease! Thanks for sharing your results as this is such a relevant area of study. If you could have changed anything about your study, what would it have been? Wishing you the best with City Year and beyond!

    1. Gracie, thank you so much! Yes, I loved how our projects interact with each other. It just goes to show that there is so much in neurodegenerative diseases and neuroscience in general that have yet to be discovered! I think I would try to make sure that I did age the flies longer next time- to implement the onset of AD longer through increased tau presence. Thank you again, Gracie! I know you are going to do great things!

  17. Interesting you pointed out the age of flies in your study – in my I.S., there was some evidence that the older our mutant larvae were, the more significant their overextension…maybe we should make a poster to hang up in around the lab that says “OLDER FLIES = DIFFERENT DATA”. Curse you, fruit flies. Anyways, awesome job!

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