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Detection of Amyloid Beta (Aβ) Oligomeric Composition Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS)

  • Jasmine S.-H. Wang
  • Shawn N. Whitehead
  • Ken K.-C. Yeung
Research Article

Abstract

The use of MALDI MS as a fast and direct method to detect the Aβ oligomers of different masses is examined in this paper. Experimental results suggest that Aβ oligomers are ionized and detected as singly charged ions, and thus, the resulting mass spectrum directly reports the oligomer size distribution. Validation experiments were performed to verify the MS data against artifacts. Mass spectra collected from modified Aβ peptides with different propensities for aggregation were compared. Generally, the relative intensities of multimers were higher from samples where oligomerization was expected to be more favorable, and vice versa. MALDI MS was also able to detect the differences in oligomeric composition before and after the incubation/oligomerization step. Such differences in sample composition were also independently confirmed with an in vitro Aβ toxicity study on primary rat cortical neurons. An additional validation was accomplished through removal of oligomers from the sample using molecular weight cutoff filters; the resulting MS data correctly reflected the removal at the expected cutoff points. The results collectively validated the ability of MALDI MS to assess the monomeric/multimeric composition of Aβ samples.

Graphical Abstract

Keywords

Alzheimer’s disease Amyloid beta-derived diffusible ligand (ADDL) Oligomers Non-covalent complexes Protein aggregation In vitro toxicity assay Embryonic rat cortical neurons 

Abbreviations

AD

Alzheimer’s disease

AFM

atomic force microscopy

amyloid beta

DMSO

dimethyl sulfoxide

ESI

electrospray ionization

F12

Ham’s F12 media

IMS

ion mobility spectrometry

MALDI

matrix-assisted laser desorption/ionization

MS

mass spectrometry

MWCO

molecular weight cutoff

NH4OH

ammonium hydroxide

SA

sinapinic acid

SPR

surface plasmon resonance

TFA

trifluoroacetic acid

TOF

time of flight

DAPI

4′-6-diamidino-2-phenylindole

Notes

Acknowledgments

The authors thank Mrs. Lynn Wang for her help with cell culture preparations. The authors also acknowledge Mrs. Kristina Jurcic, the University of Western Ontario MALDI MS Facility, and the Schulich School of Medicine and Dentistry for their support.

Author’s Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Funding Sources

This work was funded by the University of Western Ontario, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes for Health Research, Lawson Health and Research Institutes, and the Canada Foundation for Innovation.

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Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  • Jasmine S.-H. Wang
    • 1
    • 2
    • 3
  • Shawn N. Whitehead
    • 3
  • Ken K.-C. Yeung
    • 1
    • 2
  1. 1.Department of ChemistryUniversity of Western OntarioLondonCanada
  2. 2.Department of BiochemistryUniversity of Western OntarioLondonCanada
  3. 3.Vulnerable Brain Laboratory, Department of Anatomy and Cell BiologyUniversity of Western OntarioLondonCanada

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