Structure of the β-Amyloid(10 - 35) Fibril

• Published in: Journal of the American Chemical Society 2000-08, Vol.122 (33), p.7883-7889
• Main Authors: Burkoth, Timothy S, Benzinger, Tammie L. S, Urban, Volker, Morgan, David M, Gregory, David M, Thiyagarajan, P, Botto, Robert E, Meredith, Stephen C, Lynn, David G
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja000645z

The primary component of the amyloid plaques in Alzheimer's disease (AD) is a highly ordered fibril composed of the 39−43 amino acid peptide, β-amyloid (Aβ). The presence of this fibril has been correlated with both the onset and severity of the disease. Using a combination of synthetic model peptides, solid-state NMR, electron microscopy, and small angle neutron scattering (SANS), methods that allowed fibrils to be studied directly both in solution and in the solid state, the three-dimensional structure of fibrils formed from Aβ(10 - 35) is assigned. The structure consists of six laminated β-sheets propagating and twisting along the fibril axis. Each peptide strand is oriented perpendicular to the helical axis in a parallel β-sheet, with each like amino acid residue in register along the sheet. The six sheets are laminated, probably also in parallel arrays, to give a fibril with dimensions of about 60 × 80 Å. Both the methodology developed and the structural insight gained here lay the foundation for strategies to characterize and design materials capable of amyloid-like self-assembly.