Rapid characterization of amyloid-β side-chain oxidation by tandem mass spectrometry and the scoring algorithm for spectral analysis

Alexandra J. Schiewe, Lawrence Margol, Brian A. Soreghan, Stefani N. Thomas, Austin J. Yang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Purpose. Amyloid-β (Aβ) is a self-aggregating protein found in senile plaques in Alzheimer's disease (AD) brain and is thought to play a major role in the disease process. Oxidative stress may be a predominant cause of the formation of these Aβ aggregates. This study aims at identifying possible sites of copper-catalyzed oxidation of Aβ1-40 using liquid chromatography tandem mass spectrometry (LC/MS/MS) and scoring algorithm for spectral analysis (SALSA). Traditionally, identification of post-translational modifications by tandem mass spectrometric analysis requires users to inspect manually thousands of MS/MS spectra, which can be a tedious and time-consuming process. With the use of SALSA, users can automatically search for post-translational modifications based on the spacing of the m/z values associated with the ion series of an amino acid sequence. Methods. Aβ1-40 was subjected to copper-catalyzed oxidative stress. LC/MS/MS and SALSA analyses were used to determine the sites of post-translational modification within the tryptic fragments. Results. Oxidation was found to occur preferentially at the histidine residues His13 and His14 and at the methionine residue (Met35) of Aβ1-40. Conclusions. The combination of LC/MS/MS and SALSA searches could dramatically improve the efficiency and accuracy of determining the specific sites of oxidation of in vitro, copper-oxidized Aβ1-40 as well as other oxidized proteins.

Original languageEnglish (US)
Pages (from-to)1094-1102
Number of pages9
JournalPharmaceutical research
Issue number7
StatePublished - Jul 2004
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants to A. Y. from the National Institutes of Health (MH59786) and from the Pro-teomic Subcore of the USC Research Center for Liver Diseases (P30-DK48522). B. S. was supported by the Training Program in Alcoholic Liver and Pancreatic Diseases (T32 AA07578) funded by the National Institute on Alcohol Abuse and Alcoholism.


  • LC/MS/MS
  • amyloid-β
  • oxidation


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