Molecular recognition of amyloid-β oligomers in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a devastating, progressive neurodegenerative disorder that is primarily characterized by two pathologies, amyloid plaques and neurofibrillary tangles, generated from the aggregation of amyloid-β peptides (Aβ) and hyperphosphorylated tau protein, respectively. Although the exact pathogenesis of AD is still unclear, Aβ oligomers are identified as the most neurotoxic species that play pivotal roles in onset and development of AD. However, the metastable and heterogeneous nature of Aβ oligomers makes it extremely difficult to target them, resulting in the lack of high-resolution structures and toxicity mechanisms of specific oligomers. Therefore, molecular-level understanding of oligomers' propensity and behavior would be critical to propel the development of Aβ oligomer-targeted diagnostics and therapeutics in early AD. In this context, this review focuses on molecular recognition of Aβ oligomers in terms of recognition mechanism and potential applications of various targeting agents reported within the past five years. The features, limits, and potential directions of every molecular recognition strategy are also discussed.