Towards an understanding of amyloid-beta oligomers: characterization, toxicity mechanisms, and inhibitors

Abstract

Alzheimer's disease (AD) is characterized by an imbalance between production and clearance of amyloid-beta (A beta) species. Ap peptides can transform structurally from monomers into beta-stranded fibrils via multiple oligomeric states. Among the various A beta species, structured oligomers are proposed to be more toxic than fibrils; however, the identification of Ap oligomers has been challenging due to their heterogeneous and metastable nature. Multiple techniques have recently helped us gain a better understanding of oligomers' assembly details and structural properties. Moreover, some progress on elucidating the mechanisms of oligomer-triggered toxicity has been made. Based on the collection of current findings, there is growing consensus that control of toxic All oligomers could be a valid approach to regulate A beta-associated toxicity, which could advance development of new diagnostics and therapeutics for amyloid-related diseases. In this review, we summarize the recent understanding of Ap oligomers' assembly, structural properties, and toxicity, along with inhibitors against All aggregation, including oligomerization.