Acta Neuropathologica

, Volume 125, Issue 4, pp 549–564 | Cite as

Oligomers, fact or artefact? SDS-PAGE induces dimerization of β-amyloid in human brain samples

  • Andrew D. Watt
  • Keyla A. Perez
  • Alan Rembach
  • Nicki A. Sherrat
  • Lin Wai Hung
  • Timothy Johanssen
  • Catriona A. McLean
  • Woan Mei Kok
  • Craig A. Hutton
  • Michelle Fodero-Tavoletti
  • Colin L. Masters
  • Victor L. Villemagne
  • Kevin J. BarnhamEmail author
Original Paper


The formation of low-order oligomers of β-amyloid (Aβ) within the brain is widely believed to be a central component of Alzheimer’s disease (AD) pathogenesis. However, despite advances in high-throughput and high-resolution techniques such as xMAP and mass spectrometry (MS), investigations into these oligomeric species have remained reliant on low-resolution Western blots and enzyme-linked immunosorbent assays. The current investigation compared Aβ profiles within human cortical tissue using sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE), xMAP and surface enhanced laser desorption/ionization time-of-flight MS and found that whilst there was significant correlation across the techniques regarding levels of monomeric Aβ, only SDS-PAGE was capable of detecting dimeric isoforms of Aβ. The addition of synthetic di-tyrosine cross-linked Aβ1–40Met35(O) to the AD tissue demonstrated that the MS methodology was capable of observing dimeric Aβ at femto-molar concentrations, with no noticeable effect on monomeric Aβ levels. Focus turned to the association between SDS-PAGE and levels of observable dimeric Aβ within the AD brain tissue. These investigations revealed that increased levels of dimeric Aβ were observed with increasing concentrations of SDS in the sample buffer. This finding was subsequently confirmed using synthetic Aβ1–42 and suggests that SDS was inducing the formation of dimeric Aβ. The findings that SDS promotes Aβ dimerization have significant implications for the putative role of low-order oligomers in AD pathogenesis and draw into question the utility of oligomeric Aβ as a therapeutic target.


Mass spectrometry Amyloid Alzheimer’s disease Western blot Dimers Oligomers 



This work was funded by National Health and Medical Research Council of Australia.

Supplementary material

401_2013_1083_MOESM1_ESM.doc (184 kb)
Supplementary material 1 (DOC 184 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Andrew D. Watt
    • 1
    • 2
    • 3
  • Keyla A. Perez
    • 1
    • 2
  • Alan Rembach
    • 1
  • Nicki A. Sherrat
    • 2
    • 4
  • Lin Wai Hung
    • 1
    • 2
  • Timothy Johanssen
    • 1
    • 2
    • 3
  • Catriona A. McLean
    • 5
  • Woan Mei Kok
    • 2
    • 6
  • Craig A. Hutton
    • 2
    • 6
  • Michelle Fodero-Tavoletti
    • 1
    • 2
  • Colin L. Masters
    • 1
  • Victor L. Villemagne
    • 1
    • 7
  • Kevin J. Barnham
    • 1
    • 2
    • 4
    Email author
  1. 1.Mental Health Research InstituteThe University of Melbourne, ParkvilleMelbourneAustralia
  2. 2.Neuroproteomics PlatformBio21 Molecular Science and Biotechnology Institute, ParkvilleMelbourneAustralia
  3. 3.Department of PathologyThe University of Melbourne, ParkvilleMelbourneAustralia
  4. 4.Department of PharmacologyThe University of Melbourne, ParkvilleMelbourneAustralia
  5. 5.Department of Anatomical PathologyThe Alfred HospitalVictoriaAustralia
  6. 6.School of ChemistryThe University of Melbourne, ParkvilleMelbourneAustralia
  7. 7.Department of Nuclear Medicine and Centre for PETAustin HealthHeidelbergAustralia

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