Amyloid-beta oligomer (alpha-sheet conformation) (AβO (alpha-sheet))

Toxic soluble amyloid-beta (Aβ) oligomers with an alpha-sheet conformation are transient, misfolded protein aggregates implicated as the primary neurotoxic agents in Alzheimer's disease (Shea et al., 2019). While mature amyloid plaques consist of beta-sheet fibrils, structural studies suggest that the most damaging species are soluble oligomers characterized by a unique alpha-sheet secondary structure, where the peptide backbone carbonyls and amides point in opposite directions (Daggett, 2006). These alpha-sheet oligomers are known to impair long-term potentiation (LTP), disrupt cell membranes, and trigger neuroinflammation and synaptic loss (Altman et al., 2022). Because they appear early in the disease progression, they are considered a high-priority therapeutic target for early intervention. Current research focuses on developing conformation-specific binders, such as synthetic alpha-sheet peptides, to neutralize these toxic species and prevent their downstream pathological effects. Additionally, the alpha-sheet conformation serves as a basis for novel diagnostic assays, such as the Synthetic Oligomer Binding Assay (SOBA), which aims to detect Alzheimer's disease before clinical symptoms manifest (Altman et al., 2022).

Other names

Toxic Aβ oligomersAlpha-sheet amyloid-betaSoluble Aβ oligomersAβ alpha-sheet speciesAmyloid-beta protofibrils (alpha-sheet)

Conformation-specific binding and neutralization of soluble toxic oligomers to prevent synaptic damage and inhibit further aggregation into insoluble fibrils (Shea et al., 2019; Altman et al., 2022).