Determination of β-Amyloid Peptide Signatures in Cerebrospinal Fluid Using Immunoprecipitation-Mass Spectrometry
Abstract
Early pathogenic events in Alzheimer's disease (AD) involve increased production and/or reduced clearance of beta-amyloid (Abeta), especially the 42 amino acid fragment Abeta1-42. The Abeta1-42 peptide is generated through cleavage of the amyloid precursor protein by beta- and gamma-secretase and is catabolised by a variety of proteolytic enzymes such as insulin-degrading enzyme and neprilysin. Here, we describe a method that employs immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to determine the pattern of C-terminally truncated Abeta peptides in cerebrospinal fluid (CSF). Using antibodies coupled to magnetic beads, we have detected 18 C-terminally and 2 N-terminally truncated Abeta peptides in CSF. By determining the identity and profile of the truncated Abeta peptides, more insight may be gained about differences in the metabolism and structural properties of Abeta in AD. Finally, the Abeta fragment signatures may prove useful as a diagnostic test for AD.
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More than 20 additional amyloid-beta proteoforms have been detected in Alzheimer's brain samples from endogenous cleavage and post-translational modifications.
“In addition to the widely known amyloid-beta 40 and amyloid-beta 42 peptides, over 20 additional amyloid-beta proteoforms have been detected in samples of Alzheimer’s brain samples arising from endogenous cleavage and post-translational modifications.(12,13)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [12]
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Self-citation
- Authors
- Portelius, E., Westman-Brinkmalm, A., Zetterberg, H., & Blennow, K.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Institute of Clinical Neuroscience, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 43180 Mölndal, Sweden
- Corresponding author
- Portelius, Erik
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-03-10
- Volume
- 5
- Issue
- 4
- Pages
- 1010-1016
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2089765958
- Cited by
- 206
- References
- 31
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 8 · 2018: 13 · 2017: 13 · 2016: 11 · 2015: 25 · 2014: 14 · 2013: 11 · 2012: 15
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, amyloid-beta 42, cerebrospinal fluid, Alzheimer's disease, amyloid precursor protein, immunoprecipitation, MALDI-TOF mass spectrometry, amyloid metabolism, diagnostic biomarkers
- MeSH terms
- Amino Acid Sequence, Humans, Models, Biological, Molecular Sequence Data, Molecular Weight, Peptides, Precipitin Tests, Sensitivity and Specificity, Mass Spectrometry, Amyloid beta-Peptides, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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