Alzheimer's disease (AD) is a neurodegenerative disorder that affects over 5.8 million Americans each year and more globally. As the effects of this pathology are spread, medical research aims to theorize the sources of the disease in an attempt to stem its pernicious effects. Currently, there are two main theories of origin: the amyloid hypothesis and the tau hypothesis. As the amyloid hypothesis has been gradually weakened as the sole source of AD, my project focuses on the latter hypothesis, the tau hypothesis. This states that neurodegeneration results from the formation of neurofibrillary tangles (NFT), composed of hyperphosphorylated tau.

My research aims to investigate the protein phosphatase 2A pathway (PP2A), which has been introduced as a possible dephosphorylation pathway, hopefully leading to a reduction of the adverse effects of neurodegeneration caused by hyperphosphorylated tau. My model organism, Caenorhabditis elegans (strain BR5706), overexpresses tau and exhibits severe locomotion deficits. My project involves examining the effect of a PP2A enhancer, DPPE (1,2-Bisdiphenylphosphinoethane), on the locomotion of the roundworms over time.

I hypothesized that my worms would move the slowest, on average, when exposed to no chemical, but move increasing faster when exposed to the low, medium, and high dosages of DPPE, respectively. Additionally, worms exposed to no chemical should gradually decrease in locomotive velocity over time, while the treatment groups would have an overall increase in locomotive velocity, marking a reversal of the neurodegeneration.

My methods contain four main groups: (1) untreated BR5706 (M9 buffer), (2) BR5706 treated with a low (2.5 x 10-9 M) DPPE concentration, (3) BR5706 treated with a medium (5.0 x 10-9 M) DPPE concentration, and (4) BR5706 treated with a high (1.0 x 10-8 M) DPPE concentration. These four groups contain worms which have been age-synchronized (standardized in age to control for variability in locomotion at different stages of the life cycle). I then exposed the eggs to the 3 concentrations and M9 buffer (control) for a period of 3 days. In 24 hour increments, I collected the data of my measured endpoint, the locomotive velocity of the worms, by tracking the distance traveled by a particular worm in a period of 30 seconds.

After collecting my data, I analyzed my results by testing for significance between experimental groups at each time point as well as within a group across time points using a one-way ANOVA test (p <0.01). I found that my control, low, medium, and high groups were significantly different from each other at 24 and 48 hours, with an increase in locomotive velocity from the control to the high group at these time points. Additionally, my three treatment groups showed a significant increase in velocity from 0 to 3 days, while my control group showed an insignificant decrease in locomotive velocity. These results show that all treatments of the PP2A enhancer caused a significant increase in the locomotive velocity of C. elegans compared to the control, and they each showed a significant increase in velocity from 0 to 3 days, indicating that DPPE as a PP2A enhancer shows a reversal of neurodegeneration,

Future studies related to my research include comparing the effects of different PP2A enhancers and examining the effects of exposing the worms to the chemical at different stages of the life cycle.