Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A Selected Reaction Monitoring (SRM)-Based Method for Absolute Quantification of A beta(38), A beta(40), and A beta(42) in Cerebrospinal Fluid of Alzheimer's Disease Patients and Healthy Controls

Pannee, Josef ; Portelius, Erik ; Oppermann, Madalina ; Atkins, Alan ; Hornshaw, Martin ; Zegers, Ingrid ; Hojrup, Peter ; Minthon, Lennart ; Hansson, Oskar and Zetterberg, Henrik LU , et al. (2013) In Journal of Alzheimer's Disease 33(4). p.1021-1032
Abstract
Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in research centers, clinical trials, and clinical settings. However, their broad-scale use is hampered by lack of standardization across analytical platforms and by interference from binding of amyloid-beta(A beta) to matrix proteins as well as self-aggregation. Here, we report on a matrix effect-resistant method for the measurement of the AD-associated 42 amino acid species of A beta(A beta(42)), together with A beta(40) and A beta(38) in human CSF based on mass spectrometric quantification using selected reaction monitoring (SRM). Samples were prepared by solid-phase extraction and quantification was performed using stable-isotope labeled A beta... (More)
Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in research centers, clinical trials, and clinical settings. However, their broad-scale use is hampered by lack of standardization across analytical platforms and by interference from binding of amyloid-beta(A beta) to matrix proteins as well as self-aggregation. Here, we report on a matrix effect-resistant method for the measurement of the AD-associated 42 amino acid species of A beta(A beta(42)), together with A beta(40) and A beta(38) in human CSF based on mass spectrometric quantification using selected reaction monitoring (SRM). Samples were prepared by solid-phase extraction and quantification was performed using stable-isotope labeled A beta peptides as internal standards. The diagnostic performance of the method was evaluated on two independent clinical materials with research volunteers who were cognitively normal and AD patients with mild to moderate dementia. Analytical characteristics of the method include a lower limit of quantification of 62.5 pg/mL for A beta(42) and coefficients of variations below 10%. In a pilot study on AD patients and controls, we verified disease-association with decreased levels of A beta(42) similar to that obtained by ELISA and even better separation was obtained using the A beta(42)/A beta(40) ratio. The developed assay is sensitive and is not influenced by matrix effects, enabling absolute quantification of A beta(42), A beta(40), and A beta(38) in CSF, while it retains the ability to distinguish AD patients from controls. We suggest this SRM-based method for A beta peptide quantification in human CSF valuable for clinical research and trials. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyloid-beta, cerebrospinal fluid, mass, spectrometry, selected reaction monitoring
in
Journal of Alzheimer's Disease
volume
33
issue
4
pages
1021 - 1032
publisher
IOS Press
external identifiers
  • wos:000313964200011
  • scopus:84873681445
  • pmid:23076076
ISSN
1387-2877
DOI
10.3233/JAD-2012-121471
language
English
LU publication?
yes
id
29ec8147-a87c-469f-af5a-e28be42923d5 (old id 3596030)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23076076/
http://iospress.metapress.com/content/d39530n6v88742t1/fulltext.pdf
date added to LUP
2016-04-01 09:54:29
date last changed
2022-04-19 20:41:37
@article{29ec8147-a87c-469f-af5a-e28be42923d5,
  abstract     = {{Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in research centers, clinical trials, and clinical settings. However, their broad-scale use is hampered by lack of standardization across analytical platforms and by interference from binding of amyloid-beta(A beta) to matrix proteins as well as self-aggregation. Here, we report on a matrix effect-resistant method for the measurement of the AD-associated 42 amino acid species of A beta(A beta(42)), together with A beta(40) and A beta(38) in human CSF based on mass spectrometric quantification using selected reaction monitoring (SRM). Samples were prepared by solid-phase extraction and quantification was performed using stable-isotope labeled A beta peptides as internal standards. The diagnostic performance of the method was evaluated on two independent clinical materials with research volunteers who were cognitively normal and AD patients with mild to moderate dementia. Analytical characteristics of the method include a lower limit of quantification of 62.5 pg/mL for A beta(42) and coefficients of variations below 10%. In a pilot study on AD patients and controls, we verified disease-association with decreased levels of A beta(42) similar to that obtained by ELISA and even better separation was obtained using the A beta(42)/A beta(40) ratio. The developed assay is sensitive and is not influenced by matrix effects, enabling absolute quantification of A beta(42), A beta(40), and A beta(38) in CSF, while it retains the ability to distinguish AD patients from controls. We suggest this SRM-based method for A beta peptide quantification in human CSF valuable for clinical research and trials.}},
  author       = {{Pannee, Josef and Portelius, Erik and Oppermann, Madalina and Atkins, Alan and Hornshaw, Martin and Zegers, Ingrid and Hojrup, Peter and Minthon, Lennart and Hansson, Oskar and Zetterberg, Henrik and Blennow, Kaj and Gobom, Johan}},
  issn         = {{1387-2877}},
  keywords     = {{Alzheimer's disease; amyloid-beta; cerebrospinal fluid; mass; spectrometry; selected reaction monitoring}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1021--1032}},
  publisher    = {{IOS Press}},
  series       = {{Journal of Alzheimer's Disease}},
  title        = {{A Selected Reaction Monitoring (SRM)-Based Method for Absolute Quantification of A beta(38), A beta(40), and A beta(42) in Cerebrospinal Fluid of Alzheimer's Disease Patients and Healthy Controls}},
  url          = {{http://dx.doi.org/10.3233/JAD-2012-121471}},
  doi          = {{10.3233/JAD-2012-121471}},
  volume       = {{33}},
  year         = {{2013}},
}