Schedule of Events | Symposia

In-Silico Structure Analysis on Interactions Between Amyloid-Beta 42 Variants and Lecanemab

Poster Session E - Monday, March 31, 2025, 2:30 – 4:30 pm EDT, Back Bay Ballroom/Republic Ballroom

Leo Wang¹ (leohy.wang08@gmail.com); ¹Developing Virtue Secondary School

Alzheimer’s disease (AD) is characterized by cognitive decline linked to amyloid-beta 42 (Aβ42) plaque accumulation, disrupting neural networks and promoting neurotoxicity. This study investigates how specific Aβ42 mutations, such as D23N and E22G, influence binding interactions with Lecanemab, a recently approved antibody that targets Aβ42 aggregates to slow cognitive decline. Computational modeling was conducted using AlphaFold for structure prediction, ChimeraX for structural analysis, and HADDOCK for docking simulations, allowing for comparison of binding affinities and structural stability between wild-type and mutant Aβ42. Statistical analysis (e.g, ANOVA) were applied to validate differences in binding stability and affinity across various mutations with Lecanemab. Structural analysis through HADDOCK revealed that D23N significantly enhances binding stability, characterized by favorable HADDOCK scores, lower RMSD, and increased Van der Waals interactions. In contrast, the E22G mutation demonstrated reduced binding affinity, with fewer hydrogen bonds and a more flexible binding conformation. These results suggest that genetic variations in Aβ42 may impact the efficacy of Lecanemab, underscoring the potential for personalized medicine approaches in AD treatment to optimize therapeutic benefits based on individual genetic profiles. Future research should validate these computational findings experimentally, focusing on how genetic profiles may influence therapeutic responses to better target cognitive preservation strategies.

Topic Area: OTHER