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

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10 Citations (Scopus)


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
Publication statusPublished - 2018 May

Bibliographical note

Funding Information:
The support of the Agilent 6560 IM-Q-TOF instrument from Agilent Technologies is gratefully acknowledged. The synchrotron X-ray scattering measurements at 4C SAXS II beamline of the Pohang Accelerator Laboratory were supported by the Ministry of Education and Science Technology [ 55 ]. This work was supported by the National Institute of Supercomputing and Network/Korea Institute of Science and Technology Information with supercomputing resources including technical support (KSC-2016-C2-0021)

Funding Information:
This work was supported by B asic Research Program (No. 2016R1A2B4013089 ) through the National Research Foundation (NRF) of Korea (funded by the Ministry of Science, ICT, Future Planning, and Basic Science Research Program (No. 20100020209 ) through the NRF of Korea (funded by the Ministry of Education). This research was also supported by the National Research Council of Science &Technology (NST) grant by the Korea government (MSIP)(No. CAP-15-10-KRICT) and Korea University Future Re-search Grant .

Publisher Copyright:
© 2018 Elsevier B.V.


  • 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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