Liquid chromatography/tandem mass spectrometry characterization of oxidized amyloid beta peptides as potential biomarkers of Alzheimer's disease

Koichi Inoue, Carlos Garner, Bradley L. Ackermann, Tomoyuki Oe, Ian A. Blair

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Alzheimer's disease is characterized by the deposition of senile plaques that consist primarily of amyloid β peptides. There is substantial evidence that amyloid β is oxidized in vivo, which has led to the suggestion that oxidative stress is an important mediator of Alzheimer's disease. Metal-catalyzed oxidation can mimic in vivo oxidation of amyloid β because the metal ion binds to the amino acid residues at the site of oxidation, which then deliver reactive oxygen species to that site. Based on electrospray mass spectrometry, it has been suggested that metal-catalyzed oxidation occurs on histidines-13 and -14. Unfortunately, the amyloid β peptides provide complex spectra, so it is difficult to definitively characterize the sites of oxidation. Trypsin digestion of both native and oxidized amyloid β1-16 and amyloid β1-40 resulted in the formation of tryptic peptides corresponding to amyloid β6-16, which could be separated by liquid chromatography (LC). Sites of oxidation were then unequivocally characterized as histidine-13 and histidine-14 by LC/tandem mass spectrometric (MS/ MS) analysis of the tryptic peptides. The ability to analyze the specific amyloid β6-16 tryptic fragments derived from full-length amyloid β peptides will make it possible to determine whether oxidation in vivo occurs at specific histidine residues and/or at other amino acid residues such as methionine-35. Using methodology based on LC/MS/MS it will also be possible to analyze the relative amounts of oxidized peptides and native peptide in cerebrospinal fluid from patients with Alzheimer's disease as biomarkers of oxidative stress.

Original languageEnglish
Pages (from-to)911-918
Number of pages8
JournalRapid Communications in Mass Spectrometry
Volume20
Issue number5
DOIs
Publication statusPublished - 2006
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry

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