Quantitative analysis of amyloid-β peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry

Valentina Gelfanova, Richard E. Higgs, Robert A. Dean, David M. Holtzman, Martin Farlow, Eric R. Siemers, Amechand Boodhoo, Yue Wei Qian, Xiaohua He, Zhaoyan Jin, Deborah I. Fisher, Karen I. Cox, John E. Hale

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Immunoprecipitation (IP) combined with matrix-assisted laser desorption ionization (MALDI) time of flight (Tof) mass spectrometry has been used to develop quantitative assays for amyloid-β (Aβ) peptides in cerebrospinal fluid (CSF). Inclusion of 15N labelled standard peptides allows for absolute quantification of multiple Aβ isoforms in individual samples. Characterization of variability associated with all steps of the assay indicated that the IP step is the single largest contributor to overall variability. Optimization of the assay resulted in overall coefficient of variation ≤8% with high agreement to an Aβ1-40 and Aβ1-42 ELISA assay. Application of the MALDI-Tof assay to CSF obtained from healthy volunteers and Alzheimer's disease patients indicated statistically significant 43% lower levels of Aβ1-42 in the AD group (P = 0.0025).

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalBriefings in Functional Genomics and Proteomics
Volume6
Issue number2
DOIs
StatePublished - Jun 2007

Fingerprint

Cerebrospinal fluid
Immunoprecipitation
Amyloid
Ionization
Mass spectrometry
Cerebrospinal Fluid
Assays
Desorption
Mass Spectrometry
Lasers
Peptides
Chemical analysis
Healthy Volunteers
Alzheimer Disease
Protein Isoforms
Enzyme-Linked Immunosorbent Assay

Keywords

  • Alzheimers disease
  • Amyloid-β peptide
  • MALDI-Tof mass spectrometry
  • multiplexed analysis

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

Cite this

Quantitative analysis of amyloid-β peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry. / Gelfanova, Valentina; Higgs, Richard E.; Dean, Robert A.; Holtzman, David M.; Farlow, Martin; Siemers, Eric R.; Boodhoo, Amechand; Qian, Yue Wei; He, Xiaohua; Jin, Zhaoyan; Fisher, Deborah I.; Cox, Karen I.; Hale, John E.

In: Briefings in Functional Genomics and Proteomics, Vol. 6, No. 2, 06.2007, p. 149-158.

Research output: Contribution to journalArticle

Gelfanova, V, Higgs, RE, Dean, RA, Holtzman, DM, Farlow, M, Siemers, ER, Boodhoo, A, Qian, YW, He, X, Jin, Z, Fisher, DI, Cox, KI & Hale, JE 2007, 'Quantitative analysis of amyloid-β peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry', Briefings in Functional Genomics and Proteomics, vol. 6, no. 2, pp. 149-158. https://doi.org/10.1093/bfgp/elm010
Gelfanova, Valentina ; Higgs, Richard E. ; Dean, Robert A. ; Holtzman, David M. ; Farlow, Martin ; Siemers, Eric R. ; Boodhoo, Amechand ; Qian, Yue Wei ; He, Xiaohua ; Jin, Zhaoyan ; Fisher, Deborah I. ; Cox, Karen I. ; Hale, John E. / Quantitative analysis of amyloid-β peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry. In: Briefings in Functional Genomics and Proteomics. 2007 ; Vol. 6, No. 2. pp. 149-158.
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