Alzheimer's disease: Structure of aggregates revealed

Abstract

A technical feat achieved by two independent groups has enabled resolution of the molecular structure of a form of the amyloid-β protein that plays a major role in Alzheimer's disease.

Figure 1. Molecular structures of Alzheimer's-disease-associated amyloid fibrils

(a) Colvin et al. and Wälti et al. used solid-state nuclear magnetic resonance (NMR) to define very similar structures of fibrils formed by the 42-amino-acid version of amyloid-β protein (Aβ₄₂). Here, a cartoon representation of the structure from Colvin et al. (Protein Data Bank file 5KK3) is viewed down the fibril growth axis, with arrows indicating β-strand segments. (b) One Aβ₄₂ molecule from Colvin et al., in orange, is compared with one molecule from a previously determined structure of fibrils formed by the 40-amino-acid version (Aβ₄₀, Protein Data Bank file 2M4J), in blue. Ellipses indicate examples of differences in amino-acid sidechain interactions, for phenylalanine-19 (F19) and lysine-28 (K28). Residues 1-13 are omitted.