A Selected Reaction Monitoring (SRM)-Based Method for Absolute Quantification of Aβ 38 , Aβ 40 , and Aβ 42 in Cerebrospinal Fluid of Alzheimer's Disease Patients and Healthy Controls
Open accessAbstract
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-β (Aβ) 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 Aβ (Aβ 42 ), together with Aβ 40 and Aβ 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 Aβ 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 Aβ 42 and coefficients of variations below 10%. In a pilot study on AD patients and controls, we verified disease-association with decreased levels of Aβ 42 similar to that obtained by ELISA and even better separation was obtained using the Aβ 42 /Aβ 40 ratio. The developed assay is sensitive and is not influenced by matrix effects, enabling absolute quantification of Aβ 42 , Aβ 40 , and Aβ 38 in CSF, while it retains the ability to distinguish AD patients from controls. We suggest this SRM-based method for Aβ peptide quantification in human CSF valuable for clinical research and trials.
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Several studies have successfully used targeted MS strategies to quantify Aβ, tau, and APOE protein levels in CSF with similar disease-association efficacy to that of traditional ELISA assays.
“Several studies have successfully used targeted MS strategies to quantify Aβ, tau, and APOE protein levels in CSF with similar disease-association efficacy to that of traditional ELISA assays [189–191].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [189]
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- Authors
- Pannee, J., Portelius, E., Oppermann, M., Atkins, A., Hornshaw, M., Zegers, I., Höjrup, P., Minthon, L., Hansson, O., Zetterberg, H., Blennow, K., & Gobom, J.
- Affiliations
- University of Gothenburg (SE)
- Thermo Scientific, Kungens Kurva, Stockholm, Sweden
- Thermo Scientific, Hemel Hempstead, UK
- European Commission (BE)
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Lund University (SE)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Pannee, Josef
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2013-01-21
- Volume
- 33
- Issue
- 4
- Pages
- 1021-1032
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1718599092
- Cited by
- 105
- References
- 27
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 13 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 17 · 2013: 9
- FWCI
- 11.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Joint Research Centre (European Commission) (submittedVersion)
- Funders
- Alzheimer's Association
- Gun och Bertil Stohnes Stiftelse
- EU Joint Programme – Neurodegenerative Disease Research
- Wolfson Foundation
- Hjärnfonden
- Vetenskapsrådet
- Emil och Wera Cornells Stiftelse
- Demensfonden
- Sahlgrenska Akademin
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- Alzheimer's disease, amyloid-beta
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Peptide Fragments, Pilot Projects, Biomarkers, Amyloid beta-Peptides, Solid Phase Extraction, Chromatography, Reverse-Phase
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