Aducanumab Binding to Aβ_1-42 Fibrils Alters Dynamics of the N-Terminal Tail While Preserving the Fibril Core.

ABSTRACT: Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical benefit, binds selectively to aggregated Aβ via the N-terminal region. Yet, the molecular details of how the antibody engages Aβ_1-42 fibrils remain unresolved. Using magic-angle spinning nuclear magnetic resonance, we show that binding of aducanumab preserves the overall architecture of the Aβ_1-42 fibril core while inducing significant structural and dynamic perturbations in the N-terminal region. Antibody binding markedly reduces flexibility in this domain, with the appearance of sidechain resonances from residues D1, E3, and histidine (likely H6) in dipolar-based experiments. These sidechains-previously observed only in scalar-coupling spectra of the unbound state-indicate rigidificat

SUBMITTER: Palani RS 

PROVIDER: S-EPMC12637657 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature