loading page

The amyloid concentric β-barrel hypothesis: Models of amyloid beta 42 oligomers and annular protofibrils
  • Stewart Durell,
  • Rakez Kayed,
  • H, Guy
Stewart Durell
National Cancer Institute Laboratory of Cell Biology

Corresponding Author:[email protected]

Author Profile
Rakez Kayed
The University of Texas Medical Branch at Galveston Mitchell Center for Neurodegenerative Diseases
Author Profile
H, Guy
Amyloid Research Consultants (ARC) 6510 Tahawash Street Cochiti Lake NM 87083 USA
Author Profile


Amyloid beta (Aβ) peptides, a major contributor to Alzheimers disease, occur in differing lengths, each of which forms a multitude of assembly types. The most toxic soluble oligomers are formed by Aβ42; some of which have antiparallel β-sheets. Previously, our group proposed molecular models of Aβ42 hexamers in which the C-terminus third of the peptide (S3) forms an antiparallel 6-stranded β-barrel that is surrounded by an antiparallel barrel formed by the more polar N-terminus (S1) and middle (S2) portions. These hexamers were proposed to act as seeds from which dodecamers, octadecamers, both smooth and beaded annular protofibrils, and transmembrane channels form. Since then, numerous aspects of our models have been supported by experimental findings. Recently, NMR-based structures have been proposed for Aβ42 tetramers and octamers, and NMR studies have been reported for oligomers composed of ~ 32 monomers. Here we propose a range of concentric β-barrel models and compare their dimensions to image-averaged electron micrographs of both beaded annular protofibrils (bAPFs) and smooth annular protofibrils (sAPFs) of Aβ42. The smaller oligomers have 6, 8, 12, 16, and 18 monomers. These beads string together to form necklace-like bAPFs. These gradually morph into sAPFs in which a S3 β-barrel is shielded on one or both sides by β-barrels formed from S1 and S2 segments.
05 Aug 2021Submitted to PROTEINS: Structure, Function, and Bioinformatics
10 Aug 2021Submission Checks Completed
10 Aug 2021Assigned to Editor
22 Aug 2021Reviewer(s) Assigned
14 Oct 2021Review(s) Completed, Editorial Evaluation Pending
18 Oct 2021Editorial Decision: Revise Minor
28 Oct 20211st Revision Received
12 Nov 2021Assigned to Editor
12 Nov 2021Submission Checks Completed
17 Nov 2021Reviewer(s) Assigned
17 Nov 2021Review(s) Completed, Editorial Evaluation Pending
08 Dec 2021Editorial Decision: Revise Minor
31 Dec 20212nd Revision Received
02 Jan 2022Assigned to Editor
02 Jan 2022Submission Checks Completed
11 Jan 2022Review(s) Completed, Editorial Evaluation Pending
11 Jan 2022Editorial Decision: Accept
May 2022Published in Proteins: Structure, Function, and Bioinformatics volume 90 issue 5 on pages 1190-1209. 10.1002/prot.26301