Site specific NMR characterization of abeta-40 oligomers cross seeded by abeta-42 oligomers

Han Wen Chang, Ho I. Ma, Yi Shan Wu, Ming Che Lee, Eric Chung-Yueh Yuan, Shing Jong Huang, Yu Sheng Cheng, Meng Hsin Wu, Ling Hsien Tu, Jerry Chun Chung Chan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Extracellular accumulation of β amyloid peptides of 40 (Aβ40) and 42 residues (Aβ42) has been considered as one of the hallmarks in the pathology of Alzheimer's disease. In this work, we are able to prepare oligomeric aggregates of Aβ with uniform size and monomorphic structure. Our experimental design is to incubate Aβ peptides in reverse micelles (RMs) so that the peptides could aggregate only through a single nucleation process and the size of the oligomers is confined by the physical dimension of the reverse micelles. The hence obtained Aβ oligomers (AβOs) are 23 nm in diameter and they belong to the category of high molecular-weight (MW) oligomers. The solid-state NMR data revealed that Aβ40Os adopt the structural motif of β-loop-β but the chemical shifts manifested that they may be structurally different from low-MW AβOs and mature fibrils. From the thioflavin-T results, we found that high-MW Aβ42Os can accelerate the fibrillization of Aβ40 monomers. Our protocol allows performing cross-seeding experiments among oligomeric species. By comparing the chemical shifts of Aβ40Os cross seeded by Aβ42Os and those of Aβ40Os prepared in the absence of Aβ42Os, we observed that the chemical states of E11, K16, and E22 were altered, whereas the backbone conformation of the β-sheet region near the C-terminus was structurally invariant. The use of reverse micelles allows hitherto the most detailed characterization of the structural variability of Aβ40Os.

Original languageEnglish
Pages (from-to)8526-8535
Number of pages10
JournalChemical Science
Volume13
Issue number29
DOIs
Publication statusPublished - 2022 Jun 22

ASJC Scopus subject areas

  • Chemistry(all)

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