Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity

Abstract

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.

Keywords: Aggregation mechanism; Alzheimer's disease; Amyloid structure; Amyloid-β peptide; Neurotoxicity.