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Abeta CSF LC-MS

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Cerebrospinal Fluid Biomarkers

Part of the book series: Neuromethods ((NM,volume 168))

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Abstract

In this chapter, a method using an antibody independent approach based on solid phase extraction (SPE) and liquid chromatography (LC)-tandem mass spectrometry (MS/MS) is described for the analysis of Aβ isoforms in cerebrospinal fluid (CSF). Stable isotope-labeled Aβ peptides are used as internal standards, enabling absolute quantification. A high-resolution quadrupole-Orbitrap hybrid instrument was used for measurements. The method allows quantification of CSF Aβ1-42 between 150 and 4000 pg/mL.

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References

  1. Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, Cedazo-Minguez A, Dubois B, Edvardsson D, Feldman H, Fratiglioni L, Frisoni GB, Gauthier S, Georges J, Graff C, Iqbal K, Jessen F, Johansson G, Jonsson L, Kivipelto M, Knapp M, Mangialasche F, Melis R, Nordberg A, Rikkert MO, Qiu C, Sakmar TP, Scheltens P, Schneider LS, Sperling R, Tjernberg LO, Waldemar G, Wimo A, Zetterberg H (2016) Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol 15(5):455–532. https://doi.org/10.1016/S1474-4422(16)00062-4

    Article  PubMed  Google Scholar 

  2. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL (2015) Alzheimer’s disease. Nat Rev Dis Primers 1:15056. https://doi.org/10.1038/nrdp.2015.56

    Article  PubMed  Google Scholar 

  3. Blennow K, Mattsson N, Scholl M, Hansson O, Zetterberg H (2015) Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci 36(5):297–309. https://doi.org/10.1016/j.tips.2015.03.002

    Article  CAS  PubMed  Google Scholar 

  4. Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6(3):131–144. https://doi.org/10.1038/nrneurol.2010.4

    Article  CAS  Google Scholar 

  5. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S, Crutch S, Engelborghs S, Frisoni GB, Fox NC, Galasko D, Habert MO, Jicha GA, Nordberg A, Pasquier F, Rabinovici G, Robert P, Rowe C, Salloway S, Sarazin M, Epelbaum S, de Souza LC, Vellas B, Visser PJ, Schneider L, Stern Y, Scheltens P, Cummings JL (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6):614–629. https://doi.org/10.1016/S1474-4422(14)70090-0

    Article  PubMed  Google Scholar 

  6. Bjerke M, Portelius E, Minthon L, Wallin A, Anckarsater H, Anckarsater R, Andreasen N, Zetterberg H, Andreasson U, Blennow K (2010) Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid. Int J Alzheimers Dis 2010:986310. https://doi.org/10.4061/2010/986310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dumurgier J, Vercruysse O, Paquet C, Bombois S, Chaulet C, Laplanche JL, Peoc’h K, Schraen S, Pasquier F, Touchon J, Hugon J, Lehmann S, Gabelle A (2013) Intersite variability of CSF Alzheimer’s disease biomarkers in clinical setting. Alzheimers Dement 9(4):406–413. https://doi.org/10.1016/j.jalz.2012.06.006

    Article  PubMed  Google Scholar 

  8. Mattsson N, Andreasson U, Persson S, Carrillo MC, Collins S, Chalbot S, Cutler N, Dufour-Rainfray D, Fagan AM, Heegaard NH, Robin Hsiung GY, Hyman B, Iqbal K, Lachno DR, Lleo A, Lewczuk P, Molinuevo JL, Parchi P, Regeniter A, Rissman R, Rosenmann H, Sancesario G, Schroder J, Shaw LM, Teunissen CE, Trojanowski JQ, Vanderstichele H, Vandijck M, Verbeek MM, Zetterberg H, Blennow K, Kaser SA, Alzheimer’s Association QCPWG (2013) CSF biomarker variability in the Alzheimer’s association quality control program. Alzheimers Dement 9(3):251–261. https://doi.org/10.1016/j.jalz.2013.01.010

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kang JH, Korecka M, Toledo JB, Trojanowski JQ, Shaw LM (2013) Clinical utility and analytical challenges in measurement of cerebrospinal fluid amyloid-beta1-42 and tau proteins as Alzheimer disease biomarkers. Clin Chem 59(6):903–916. https://doi.org/10.1373/clinchem.2013.202937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mattsson N, Zegers I, Andreasson U, Bjerke M, Blankenstein MA, Bowser R, Carrillo MC, Gobom J, Heath T, Jenkins R, Jeromin A, Kaplow J, Kidd D, Laterza OF, Lockhart A, Lunn MP, Martone RL, Mills K, Pannee J, Ratcliffe M, Shaw LM, Simon AJ, Soares H, Teunissen CE, Verbeek MM, Umek RM, Vanderstichele H, Zetterberg H, Blennow K, Portelius E (2012) Reference measurement procedures for Alzheimer’s disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid beta42. Biomark Med 6(4):409–417. https://doi.org/10.2217/bmm.12.39

    Article  CAS  PubMed  Google Scholar 

  11. Leinenbach A, Pannee J, Dulffer T, Huber A, Bittner T, Andreasson U, Gobom J, Zetterberg H, Kobold U, Portelius E, Blennow K, IFCC Scientific Division Working Group on CSF Proteins (2014) Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-beta in cerebrospinal fluid. Clin Chem 60(7):987–994. https://doi.org/10.1373/clinchem.2013.220392

    Article  CAS  PubMed  Google Scholar 

  12. Ahmadkhaniha R, Shafiee A, Rastkari N, Kobarfard F (2009) Accurate quantification of endogenous androgenic steroids in cattle’s meat by gas chromatography mass spectrometry using a surrogate analyte approach. Anal Chim Acta 631(1):80–86. https://doi.org/10.1016/j.aca.2008.10.011

    Article  CAS  PubMed  Google Scholar 

  13. Jemal M, Schuster A, Whigan DB (2003) Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard. Rapid Commun Mass Spectrometry 17(15):1723–1734. https://doi.org/10.1002/rcm.1112

    Article  CAS  Google Scholar 

  14. Li W, Cohen LH (2003) Quantitation of endogenous analytes in biofluid without a true blank matrix. Anal Chem 75(21):5854–5859. https://doi.org/10.1021/ac034505u

    Article  CAS  PubMed  Google Scholar 

  15. Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W, ElMoualij B, Schraen S, Moreaud O, Gabelle A, Thouvenot E, Thomas-Anterion C, Touchon J, Krolak-Salmon P, Kovacs GG, Coudreuse A, Quadrio I, Lehmann S (2012) Cerebrospinal fluid collection tubes: a critical issue for Alzheimer disease diagnosis. Clin Chem 58(4):787–789. https://doi.org/10.1373/clinchem.2011.178368

    Article  CAS  PubMed  Google Scholar 

  16. Lewczuk P, Beck G, Esselmann H, Bruckmoser R, Zimmermann R, Fiszer M, Bibl M, Maler JM, Kornhuber J, Wiltfang J (2006) Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid beta peptides. Clin Chem 52(2):332–334. https://doi.org/10.1373/clinchem.2005.058776

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden

    Josef Pannee & Kaj Blennow

  2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

    Josef Pannee & Kaj Blennow

  3. Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothernburg, Mölndal, Sweden

    Henrik Zetterberg

Authors
  1. Josef Pannee
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  2. Kaj Blennow
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  3. Henrik Zetterberg
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Corresponding author

Correspondence to Josef Pannee .

Editor information

Editors and Affiliations

  1. Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands

    Charlotte E. Teunissen

  2. Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothernburg, Mölndal, Sweden

    Henrik Zetterberg

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Pannee, J., Blennow, K., Zetterberg, H. (2021). Abeta CSF LC-MS. In: Teunissen, C.E., Zetterberg, H. (eds) Cerebrospinal Fluid Biomarkers. Neuromethods, vol 168. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1319-1_4

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  • DOI: https://doi.org/10.1007/978-1-0716-1319-1_4

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1318-4

  • Online ISBN: 978-1-0716-1319-1

  • eBook Packages: Springer Protocols

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