The Pathogenesis of Alzheimer’s Disease.

This is part of a series of posts by recipients of the 2021 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here.

This entry is by Eric Gao, COL ’24

My name is Eric Gao and I am a rising sophomore at the University of Pennsylvania. I am currently majoring in biochemistry and am a member of the Vagelos Molecular Life Sciences program. This summer I worked with Dr. Axelsen, who studies the pathogenesis of Alzheimer’s Disease.

My summer research project involved quantifying the rate at which amyloid beta proteins aggregate. Amyloid beta proteins form plaques in the brain when they aggregate, which disrupts neural connections and cellular communication. This seems to cause the symptoms of memory loss and confusion experienced by those with Alzheimer’s Disease. As such, my project involved preparing amyloid beta protein in order to have it fibrilize and observe the rate at which it does so. This was done through the usage of a stain, Thioflavin T, and a fluorescence spectrometer. Thioflavin T specifically binds to amyloid beta fibrils but not the monomer, and when it binds to the fibrils its fluorescence increases dramatically. As such, by observing how the fluorescence increases over the course of the incubation period we can measure how quickly the proteins aggregate. I will also be looking into how HNE, 4-Hydroxynonenal, affects the rate of fibrillization by adding it in various concentrations to the amyloid beta samples.

The true cause behind Alzheimer’s and the aggregation of amyloid beta proteins in the brain is still not fully understood, but the two seem to be related. As such, by understanding how and why amyloid beta proteins aggregate, we may be a step closer to creating better treatments for Alzheimer’s Disease. HNE is important as it is formed from the oxidation of omega-6 polyunsaturated fatty acids, a molecule we find in our brains and foods thought to be healthy for humans. If it definitively speeds up the rate of amyloid beta aggregation then it may be a factor behind what leads to Alzheimer’s Disease.

My research experience has been an incredible introduction to all the equipment in a laboratory, which I have not worked with before. This includes using pipettes, plasma cleaners, lyophilizers, and even properly keeping a lab notebook. I learned how to use machines such as a spectrophotometer and fluorescence spectrometer as well, which often introduced challenges for me as I ran into a multitude of minor troubleshooting issues. It forced me to think creatively in order to master the software and understand how the machine properly operates. Going through the incubation procedure of the proteins was challenging as well and required me to utilize all the knowledge I had gained throughout my experience to successfully create the fibrils.

Furthermore, I improved at searching for and comprehending scientific papers, which was important as I had to plan how to prepare the amyloid beta fibrils by looking through previous literature. Overall, I have a much better understanding of how research is conducted in the professional setting and have deepened my knowledge in both Alzheimer’s Disease and laboratory procedures

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