Sterol-activated amyloid beta fibril formation.

ABSTRACT: The metabolic processes that link Alzheimer's disease (AD) to elevated cholesterol levels in the brain are not fully defined. Amyloid beta (Aβ) plaque accumulation is believed to begin decades prior to symptoms and to contribute significantly to the disease. Cholesterol and its metabolites accelerate plaque formation through as-yet-undefined mechanisms. Here, the mechanism of cholesterol (CH) and cholesterol 3-sulfate (CS) induced acceleration of Aβ₄₂ fibril formation is examined in quantitative ligand binding, Aβ₄₂ fibril polymerization, and molecular dynamics studies. Equilibrium and pre-steady-state binding studies reveal that monomeric Aβ₄₂•ligand complexes form and dissociate rapidly relative to oligomerization, that the ligand/peptide stoichiometry is

SUBMITTER: Cook I 

PROVIDER: S-EPMC10704437 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature