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 R. Farlow; Eric R. Siemers; Amechand Boodhoo; Yue Wei Qian; Xiaohua He; Zhaoyan Jin; Deborah I. Fisher; Karen I. Cox; John E. Hale

doi:10.1093/bfgp/elm010

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 R. Farlow, Eric R. Siemers, Amechand Boodhoo, Yue Wei Qian, Xiaohua He, Zhaoyan Jin, Deborah I. Fisher, Karen I. Cox, John E. Hale

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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 Aβ_1-40 and Aβ_1-42 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 Aβ_1-42 in the AD group (P = 0.0025).

Original language	English
Pages (from-to)	149-158
Number of pages	10
Journal	Briefings in Functional Genomics and Proteomics
Volume	6
Issue number	2
DOIs	https://doi.org/10.1093/bfgp/elm010
State	Published - Jun 2007

Keywords

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

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Gelfanova, V., Higgs, R. E., Dean, R. A., Holtzman, D. M., Farlow, M. R., Siemers, E. R., Boodhoo, A., Qian, Y. W., He, X., Jin, Z., Fisher, D. I., Cox, K. I., & Hale, J. E. (2007). Quantitative analysis of amyloid-β peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry. Briefings in Functional Genomics and Proteomics, 6(2), 149-158. https://doi.org/10.1093/bfgp/elm010

@article{768ef8bfcb4447b28c5cfed902b0dcc2,

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

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).",

keywords = "Alzheimers disease, Amyloid-β peptide, MALDI-Tof mass spectrometry, multiplexed analysis",

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

year = "2007",

month = jun,

doi = "10.1093/bfgp/elm010",

language = "English",

volume = "6",

pages = "149--158",

journal = "Briefings in Functional Genomics and Proteomics",

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number = "2",

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Gelfanova, V, Higgs, RE, Dean, RA, Holtzman, DM, Farlow, MR, 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

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T1 - Quantitative analysis of amyloid-β peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry

AU - Gelfanova, Valentina

AU - Higgs, Richard E.

AU - Dean, Robert A.

AU - Holtzman, David M.

AU - Farlow, Martin R.

AU - Siemers, Eric R.

AU - Boodhoo, Amechand

AU - Qian, Yue Wei

AU - He, Xiaohua

AU - Jin, Zhaoyan

AU - Fisher, Deborah I.

AU - Cox, Karen I.

AU - Hale, John E.

PY - 2007/6

Y1 - 2007/6

N2 - 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).

AB - 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).

KW - Alzheimers disease

KW - Amyloid-β peptide

KW - MALDI-Tof mass spectrometry

KW - multiplexed analysis

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JO - Briefings in Functional Genomics and Proteomics

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ER -

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

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