Aβ42 oligomers can seed the fibrillization of Aβ40 peptides

• Published in: Journal of the Chinese Chemical Society (Taipei) Vol. 69; no. 8; pp. 1318 - 1325
• Main Authors: Wu, Yi‐Shan, Huang, Shing‐Jong, Wu, Meng‐Hsin, Tu, Ling‐Hsien, Lee, Ming‐Che, Chan, Jerry Chun Chung
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley‐VCH Verlag GmbH & Co. KGaA 01.08.2022; Wiley Subscription Services, Inc
• Subjects: Agglomeration; Aggregates; Alzheimer's disease; beta amyloid; cross seeding; Molecular structure; NMR; Nuclear magnetic resonance; Oligomers; Peptides; Reverse micelles; solid‐state NMR; Sulfosuccinates
• ISSN: 0009-4536; 2192-6549
• DOI: 10.1002/jccs.202200136

Aggregation of Aβ40 and Aβ42 are considered as pivotal players in the pathogenic mechanism of Alzheimer's disease. In this work, we applied reverse micelles formed by sodium bis(2‐ethylhexyl) sulfosuccinate (AOT) to prepare oligomeric aggregates of Aβ40 or Aβ42 peptides. The resultant globular aggregates were approximately 22 nm in diameter and they were capable to form mature fibrils upon self‐aggregation. Furthermore, we found that the Aβ42 oligomeric aggregates can seed the fibrillization of Aβ40 monomers. Solid‐state NMR results revealed that the Aβ40 fibrils seeded by Aβ40 or Aβ42 oligomers adopt a similar molecular structure for the residues near the C‐terminus. The molecular structures of Aβ40 fibrils seeded by Aβ42 oligomers are similar to those seeded by Aβ40 oligomers in the β2 region.