Chameleonic Nature of Aβ: Implications for Alzheimer's and Other Amyloid Diseases

Abstract

The amyloid-β peptide (Aβ), implicated in Alzheimer's disease, exhibits significant polymorphism. At the monomer level, Aβ can adopt disordered, helical, and β-hairpin structures, influenced by environmental conditions. Both oligomeric and fibrillar states, characterized by the prevalence of β-sheets, are polymorphic in the arrangement of β-strands. This chameleon-like behavior arises from Aβ’s unique sequence and relatively flat energy landscape, which facilitates aggregation and may contribute to the prevalence of Alzheimer's disease, while also enabling disaggregation, thus slowing disease progression. In contrast, Creutzfeldt-Jakob disease, which is much rarer, progresses far more rapidly, likely due to the steeper energy landscape of the prion protein.