The amyloid‐β peptide in Alzheimer's disease: molecular interactions and structure conversions

Abstract

The amyloid β (Aβ) peptide consists of 39–43 residues and is the major component of the neuritic plaques in the brains of Alzheimer's disease (AD) patients. It is possible to study the peptide self‐aggregation process (“amyloid formation”, structures and kinetics) using biophysical methods such as NMR, fluorescence or CD spectroscopy. The interactions of Aβ(1–40) with small molecules, or metal ions such as Zn(II) or Cu(II), that modulate the aggregation process can be studied in semi‐stationary states by these methods. Kinetic effects on the amyloid formation process can be followed by fluorescence, after labeling the material rich in β‐structure by the amyloid‐specific dye Thioflavin T. The β‐hairpin structure of the peptide with a mainly unstructured N‐terminus appears to be a basic unit for formation of the larger amyloid structures associated with insoluble fibrils. Smaller oligomeric peptide aggregates, possibly the major cell toxic agents, can be studied by Soft Ionization Mass Spectrometry.Fluorescence Correlation Spectroscopy (FCS) shows the heterogeneity of the aggregation process of ThT‐labeled Aβ, in terms of time dependent amyloid aggregate sizes, on a single particle level. Modulation of the amyloid formation by Zn(II) or Cu(II) ions binding to specific residues in the N‐terminus of the Aβ peptide can be followed by the biophysical methods, showing changes in structures as well as kinetics for the aggregation process.Understanding the basic properties and reactions of the major participants in the chemical processes leading to AD gives a firm basis for the future development of agents that may be used in therapies against AD.Support or Funding InformationThe Swedish Research Council, The Alzheimer Foundation, The Magn. Bergvall FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.