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Background

Oligomers of Amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer's disease (AD). However, the heterogeneous and dynamic nature of AβO, and inadequate markers for AβO subtypes, have stymied effective AβO identification and therapeutic targeting in vivo. We identified an AβO-subclass epitope defined by constrained sidechain orientation of serine-asparagine-lysine (cSNK), not displayed by Aβ monomers and fibrils.

Methods

Molecular dynamics simulations confirmed the epitope restriction of cSNK to AβOs. Specificity of a mouse monoclonal antibody raised against the AβO cSNK epitope was evaluated by surface plasmon resonance (SPR), dot blotting/immunoblotting, immunoprecipitation, immunohistochemistry and immunoelectron microscopy. The percent of AβO falling into the cSNK subclass was defined by acute peripheral infusion of anti-AβO cSNK in aged …