Late Breaking Original Research
Monday, November 13, 2023
01:00 PM–02:30 PM
Abstract
Introduction: The accumulation of amyloid-ß (Aß) peptide and hyperphosphorylation of tau protein are thought to contribute to the pathogenesis of Alzheimer’s Disease (AD). Studies in recent years have shown that certain small molecules can inhibit the formation of Aß42 peptides into oligomers and plaques. Some recently synthesized curcumin analogues displayed sub-micromolar activity
in vitro, towards Aß aggregation; however, these were not tested in any animal model.
Research Question or Hypothesis: Novel anti-amyloidogenic agents will lead to improved lifespan and/or locomotion, when tested on Aß transgenic Drosophila melanogaster.
Study Design: nSyb-Gal4 was crossed with UAS-Aß42 to generate a transgenic line of interest. Compounds A, B, and C, in concentrations of 1, 10, and 100 µg each, per 8 mL of fly food, were used to test the compounds’ effectiveness in adult flies (n=10).
Methods: Compound effectiveness was assessed by performing the lifespan (log-rank test) and forced climbing assay (two-way ANOVA). The assessment of Aß42 peptide accumulation in the brains of the flies treated and untreated with compounds was quantified via ELISA.
Results: The lifespan of anti-amyloidogenic agent-fed treatment groups did not differ significantly compared to the control group. However, treatment groups performed better on the forced climbing assay, by up to 68% when fed Compound B (1 µg) indicating improved locomotor activity. Preliminary ELISA data (n=1) indicates no alteration in Aß42 generation regardless of compound or concentration differences.
Conclusion: Compound A and C did not show a statistically significant difference in lifespan and locomotor activity compared to control. However, Compound B showed a statistically significant improvement in locomotion while still maintaining the same level of Aß42 accumulation in the brain, indicating its use as a potential agent in AD. Future studies will be repeated to confirm results.
Presenting Author
Paul Beak PharmD '24 Candidate, BAMCPHS University-Boston
Authors
Greg Landry PhD, DABT
MCPHS University-Boston
Ronny Priefer PhD
Massachusetts College of Pharmacy and Health Sciences (MCPHS) University