Competitive homo- and hetero- self-assembly of amyloid-β 1–42 and 1–40 in the early stage of fibrillation

Chae Eun Heo, Tae Su Choi, Hugh I. Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Amyloid-β 1–42 (Aβ42) and 1–40 (Aβ40) peptides, whose self-assembly process has been linked with the formation of amyloid plaques in Alzheimer's disease, exist as a mixture in human fluids. For this reason, heteromeric self-assembly of Aβ42 and Aβ40 has been widely investigated to understand the influence of this mixture in Aβ fibrillation. However, understanding the role of heteromeric self-assembly in Aβ fibrillation is a challenge owing to the heterogeneous cross-interactions between Aβ42 and Aβ40. Herein, we demonstrated the influence of the cross-interaction of Aβ42 and Aβ40 in the early stage of fibrillation using electrospray ionization mass spectrometry (ESI–MS) and drift tube ion mobility spectrometry (DTIMS) along with solution small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations. In the mixture of Aβ42 and Aβ40, Aβ42 has only a slight preference for homo-oligomerization versus hetero-oligomerization with Aβ40 (∼1–2 fold) when forming small oligomers (from dimer to tetramer) in the early stage of fibrillation. However, the cross-interaction is gradually attenuated as oligomerization proceeds because of the different conformations in the Aβ42 and Aβ40 assemblies. Consequently, the competitive self-assembly of Aβ42 and Aβ40 can disturb the homo-oligomerization of Aβ42 in the early stage of fibrillation, whereas Aβ42 and Aβ40 species prefer the independent self-assembly after the early stage.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalInternational Journal of Mass Spectrometry
Volume428
DOIs
Publication statusPublished - 2018 May 1

Keywords

  • Alzheimer's disease
  • Cross-interaction
  • Drift tube ion mobility spectrometry
  • Electrospray ionization-mass spectrometry
  • Solution small-angle X-ray scattering

ASJC Scopus subject areas

  • Instrumentation
  • Condensed Matter Physics
  • Spectroscopy
  • Physical and Theoretical Chemistry

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