Method for the simultaneous quantitation of apolipoprotein E isoforms using tandem mass spectrometry
Open accessAbstract
Using apolipoprotein E (ApoE) as a model protein, we developed a protein isoform analysis method utilizing stable isotope labeling tandem mass spectrometry (SILT MS). ApoE isoforms are quantitated using the intensities of the b and y ions of the (13)C-labeled tryptic isoform-specific peptides versus unlabeled tryptic isoform-specific peptides. The ApoE protein isoform analysis using SILT allows for the simultaneous detection and relative quantitation of different ApoE isoforms from the same sample. This method provides a less biased assessment of ApoE isoforms compared to antibody-dependent methods, and may lead to a better understanding of the biological differences between isoforms.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The ApoE isoform-specific liquid chromatography/mass spectrometry method used is valid for distinguishing ApoE isoforms.
“Utilizing an ApoE isoform-specific liquid chromatography/mass spectrometry (LC/MS) method [29], we compared ApoE isoform kinetics in both homozygous and heterozygous subjects in the periphery and CNS.”
From In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS (2012) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Functional and quantitative proteomics using SILAC
Mann, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2067 · Cited by 931 · see citing works
Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo
Bateman, R. J., Munsell, L. Y., Morris, J. C., Swarm, R., Yarasheski, K. E., & Holtzman, D. M. (2006) · Nature Medicine · doi:10.1038/nm1438 · Cited by 599 · see citing works
Self-citationApolipoprotein E structure: insights into function
Hatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.06.008 · Cited by 583 · see citing works
Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis
Wolfe, R. R., & Chinkes, D. L. (2004) · Medical Entomology and Zoology · Cited by 497 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
A γ‐secretase inhibitor decreases amyloid‐β production in the central nervous system
Bateman, R. J., Siemers, E. R., Mawuenyega, K. G., Wen, G., Browning, K. R., Sigurdson, W. C., Yarasheski, K. E., Friedrich, S. W., DeMattos, R. B., May, P. C., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21623 · Cited by 322 · see citing works
Self-citationDoherty, M. K., Whitehead, C. C., McCormack, H., Gaskell, S. J., & Beynon, R. J. (2005) · PROTEOMICS · doi:10.1002/pmic.200400959 · Cited by 165 · see citing works
15N Metabolic Labeling of Mammalian Tissue with Slow Protein Turnover
McClatchy, D. B., Dong, M., Wu, C. C., Venable, J. D., & Yates, J. R. (2007) · Journal of Proteome Research · doi:10.1021/pr060599n · Cited by 151 · see citing works
Morikawa, M., Fryer, J. D., Sullivan, P. M., Christopher, E., Schindler, S. E., Demattos, R. B., Odell, M., Fagan, A. M., Lashuel, H. A., Walz, T., et al. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.11.005 · Cited by 136 · see citing works
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
Bateman, R. J., Munsell, L. Y., Chen, X., Holtzman, D. M., & Yarasheski, K. E. (2007) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2007.02.009 · Cited by 76 · see citing works
Self-citationIncorporation of a stable isotopically labeled amino acid into multiple human apolipoproteins.
Patterson, B. W., Hachey, D., Cook, G., Amann, J., & Klein, P. (1991) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41970-4 · Cited by 71 · see citing works
Fukumoto, H., Ingelsson, M., Gårevik, N., Wahlund, L.-O., Nukina, N., Yaguchi, Y., Shibata, M., Hyman, B. T., Rebeck, G. W., & Irizarry, M. C. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00088-8 · Cited by 63 · see citing works
Molina, H., Parmigiani, G., & Pandey, A. (2005) · Analytical Chemistry · doi:10.1021/ac048204b · Cited by 24 · see citing works
Elbert, D. L., Mawuenyega, K. G., Scott, E. A., Wildsmith, K. R., & Bateman, R. J. (2008) · Journal of Proteome Research · doi:10.1021/pr800386u · Cited by 16 · see citing works
Self-citationSato, T., Ishihama, Y., & Oda, Y. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-255-7_4 · Cited by 10 · see citing works
In-vivo metabolism of VLDL-apolipoprotein-B, -CIII and -E in normolipidemic subjects
Dinkel, R. E., Barrett, P. H. R., Demant, T., & Parhofer, K. G. (2005) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2005.06.004 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
van den Broek, I., Romijn, F. P. H. T. M., Nouta, J., van der Laarse, A., Drijfhout, J. W., Smit, N. P. M., van der Burgt, Y. E. M., & Cobbaert, C. M. (2016) · Clinical Chemistry · doi:10.1373/clinchem.2015.246702 · Cited by 105 · see citing works
Simon, R., Girod, M., Fonbonne, C., Salvador, A., Clément, Y., Lantéri, P., Amouyel, P., Lambert, J. C., & Lemoine, J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.018861 · Cited by 92 · see citing works
Ghosal, K., Haag, M., Verghese, P. B., West, T., Veenstra, T., Braunstein, J. B., Bateman, R. J., Holtzman, D. M., & Landreth, G. E. (2016) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2016.06.001 · Cited by 73 · see citing works
Self-citationMartínez‐Morillo, E., Nielsen, H. M., Batruch, I., Drabovich, A. P., Begcevic, I., Lopez, M. F., Minthon, L., Bu, G., Mattsson, N., Portelius, E., et al. (2014) · Journal of Proteome Research · doi:10.1021/pr401060x · Cited by 67 · see citing works
Clinical protein mass spectrometry
Scherl, A. (2015) · Methods · doi:10.1016/j.ymeth.2015.02.015 · Cited by 63 · see citing works
Lehmann, S., Hoofnagle, A. N., Hochstrasser, D. F., Brede, C., Glueckmann, M., Cocho, J. A., Ceglarek, U., Lenz, C., Vialaret, J., Scherl, A., et al. (2012) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2012-0723 · Cited by 59 · see citing works
Minta, K., Brinkmalm, G., Janelidze, S., Sjödin, S., Portelius, E., Stomrud, E., Zetterberg, H., Blennow, K., Hansson, O., & Andréasson, U. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00585-7 · Cited by 55 · see citing works
Baker-Nigh, A. T., Mawuenyega, K. G., Bollinger, J. G., Ovod, V., Kasten, T., Franklin, E. E., Liao, F., Jiang, H., Holtzman, D., Cairns, N. J., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.721779 · Cited by 54 · see citing works
Self-citationIn Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS
Wildsmith, K. R., Basak, J. M., Patterson, B. W., Pyatkivskyy, Y., Kim, J., Yarasheski, K. E., Wang, J. X., Mawuenyega, K. G., Jiang, H., Parsadanian, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038013 · Cited by 54 · see citing works
“Utilizing an ApoE isoform-specific liquid chromatography/mass spectrometry (LC/MS) method [29], we compared ApoE isoform kinetics in both homozygous and heterozygous subjects in the periphery and CNS.”
MethodInfluentialSelf-citationProteoforms and their expanding role in laboratory medicine
Forgrave, L. M., Wang, M., Yang, D., & DeMarco, M. L. (2021) · Practical Laboratory Medicine · doi:10.1016/j.plabm.2021.e00260 · Cited by 46 · see citing works
Giannisis, A., Al-Grety, A., Carlsson, H., Patra, K., Twohig, D., Sando, S. B., Lauridsen, C., Berge, G., Grøntvedt, G. R., Bråthen, G., et al. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01058-9 · Cited by 46 · see citing works
Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study
Blanchard, V., Ramin-Mangata, S., Billon-Crossouard, S., Aguesse, A., Durand, M., Chemello, K., Nativel, B., Flet, L., Chétiveaux, M., Jacobi, D., et al. (2018) · Journal of Lipid Research · doi:10.1194/jlr.p083576 · Cited by 43 · see citing works
Rezeli, M., Zetterberg, H., Blennow, K., Brinkmalm, A., Laurell, T., Hansson, O., & Marko‐Varga, G. (2015) · EuPA Open Proteomics · doi:10.1016/j.euprot.2015.07.012 · Cited by 43 · see citing works
Advantageous Uses of Mass Spectrometry for the Quantification of Proteins
Hale, J. E. (2013) · International Journal of Proteomics · doi:10.1155/2013/219452 · Cited by 31 · see citing works
Advances in quantifying apolipoproteins using LC-MS/MS technology: implications for the clinic
van den Broek, I., Sobhani, K., & Eyk, J. E. V. (2017) · Expert Review of Proteomics · doi:10.1080/14789450.2017.1374859 · Cited by 29 · see citing works
The role of apolipoprotein E in neurodegeneration and cardiovascular disease
Lopez, M. F., Krastins, B., & Ning, M. (2014) · Expert Review of Proteomics · doi:10.1586/14789450.2014.901892 · Cited by 24 · see citing works
Holzmann, J., Fuchs, J., Pichler, P., Peters, J., & Mechtler, K. (2010) · Journal of Proteome Research · doi:10.1021/pr100927x · Cited by 23 · see citing works
Wang, M., Chen, J., & Turko, I. V. (2012) · Analytical Chemistry · doi:10.1021/ac3018873 · Cited by 23 · see citing works
Hirtz, C., Vialaret, J., Nouadje, G., Schraen‐Maschke, S., Benlian, P., Mary, S., Philibert, P., Tiers, L., Bros, P., Delaby, C., et al. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.12.020 · Cited by 23 · see citing works
Uen, Y., Liao, C.-C., Lin, J.-C., Pan, Y.-H., Liu, Y., Chen, Y.-C., Chen, W.-J., Tai, C.-C., Lee, K.-W., Liu, Y., et al. (2015) · Journal of Proteomics · doi:10.1016/j.jprot.2015.05.038 · Cited by 20 · see citing works
Begcevic Brkovic, I., Zöhrer, B., Scholz, M., Reinicke, M., Dittrich, J., Kamalsada, S., Baber, R., Beutner, F., Teren, A., Engel, C., et al. (2022) · Nutrients · doi:10.3390/nu14122474 · Cited by 13 · see citing works
Genome-wide Screen for Modulation of Hepatic Apolipoprotein A-I (ApoA-I) Secretion
Miles, R. R., Perry, W., Haas, J. V., Mosior, M. K., N'Cho, M., Wang, J. J., Yu, P., Calley, J. N., Yue, Y. G., Carter, Q. L., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.410092 · Cited by 12 · see citing works
Self-citationRegulatory context and validation of assays for clinical mass spectrometry proteomics (cMSP) methods
Hirtz, C., Bros, P., Brede, C., Lescuyer, P., Maceski, A. M., Vialaret, J., Delatour, V., & Lehmann, S. (2018) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2018.1470159 · Cited by 11 · see citing works
Recruitment of apolipoprotein E facilitates Herpes simplex virus 1 attachment and release
Liu, L., Bano, F., Conca, D. V., Thorsteinsson, K., Jayaweera, S. W., Avinens, D., Pace, H. P., Lövheim, H., Olofsson, A., & Bally, M. (2025) · npj Viruses · doi:10.1038/s44298-025-00099-9 · Cited by 8 · see citing works
Human Apolipoprotein E Resequencing by Proteomic Analysis and Its Application to Serotyping
Nishimura, M., Satoh, M., Nishimura, S., Kakinuma, S., Sato, K., Sawai, S., Tsuchida, S., Kazama, T., Matsushita, K., Kado, S., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085356 · Cited by 6 · see citing works
Lehmann, S. (2015) · Journal of Proteomics & Bioinformatics · doi:10.4172/jpb.s5-003 · Cited by 4 · see citing works
Correction: In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS
Wildsmith, K. R., Basak, J. M., Patterson, B. W., Pyatkivskyy, Y., Kim, J., Yarasheski, K. E., Wang, J. X., Mawuenyega, K. G., Jiang, H., Parsadanian, M., et al. (2012) · PLoS ONE · doi:10.1371/annotation/9bd329b7-cdea-45ec-a4aa-a173855dc0b9 · Cited by 4 · see citing works
Self-citationReply to: Fractional synthesis and clearance rates for amyloid β
Elbert, D. L., Patterson, B. W., Ercole, L., Ovod, V., Kasten, T., Mawuenyega, K., Yarasheski, K., Morris, J. C., Benzinger, T., Holtzman, D. M., et al. (2011) · Nature Medicine · doi:10.1038/nm.2496 · Cited by 3 · see citing works
Self-citationWu, T., Xi, X., Chen, Y., Jiang, C., Zhang, Q., Dai, G., Bai, Y., Zhang, W., Ni, T., Zou, J., et al. (2021) · Journal of Separation Science · doi:10.1002/jssc.202100066 · Cited by 1 · see citing works
Nishimura, M., Satoh, M., Matsushita, K., & Nomura, F. (2014) · Expert Review of Proteomics · doi:10.1586/14789450.2014.936390 · Cited by 1 · see citing works
Current literature in mass spectrometry
(2010) · Journal of Mass Spectrometry · doi:10.1002/jms.1651
- Authors
- Wildsmith, K. R., Han, B., & Bateman, R. J.
- Affiliations
- Washington University in St. Louis (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Bateman, Randall J.
- Venue
- Analytical Biochemistry
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 395
- Issue
- 1
- Pages
- 116-118
- ISSN
- 0003-2697 (ISSN-L)
- PMC
- PMC2749897
- OpenAlex
- W1984525664
- Cited by
- 31
- References
- 18
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Analytical Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K23AG030946)
- National Institute of Neurological Disorders and Stroke (R01NS065667)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- apolipoprotein E, protein isoforms, stable isotope labeling, tandem mass spectrometry, tryptic peptides, relative quantification
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Astrocytes, Carbon Isotopes, Cell Line, Transformed, Indicator Dilution Techniques, Lipoproteins, Peptide Fragments, Risk Factors, Trypsin, Protein Isoforms, Mice, Apolipoprotein E4, Apolipoprotein E2, Tandem Mass Spectrometry, Gene Knock-In Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
