Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Translational Neuroscience

Editor-in-Chief: David, Olivier

IMPACT FACTOR 2017: 0.833
5-year IMPACT FACTOR: 1.247

CiteScore 2017: 1.00

SCImago Journal Rank (SJR) 2017: 0.428
Source Normalized Impact per Paper (SNIP) 2017: 0.244

Open Access
See all formats and pricing
More options …

Comparison of two commercial enzyme-linked immunosorbent assays for cerebrospinal fluid measurement of amyloid β1–42 and total tau

Mirjana Babić
  • Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Šalata 12, 10000, Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Željka Vogrinc
  • Laboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andrea Diana
  • Laboratory of Neurogenesis and Neuropoiesis, Department of Biomedical Sciences, University of Cagliari, Città Universitaria di Monserrato, 09042, Monserrato (Cagliari), Italy
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nataša Klepac
  • Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb Medical School, University Hospital Center Zagreb, Šalata 2, 10000, Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Fran Borovečki
  • Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb Medical School, University Hospital Center Zagreb, Šalata 2, 10000, Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Patrick Hof
  • Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Goran Šimić
  • Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Šalata 12, 10000, Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-06-09 | DOI: https://doi.org/10.2478/s13380-013-0123-4


Amyloid β1–42 (Aβ1–42), total tau (t-tau), and phosphorylated tau (p-tau) are the main cerebrospinal fluid (CSF) biomarkers for early diagnosis of Alzheimer’s disease (AD). Detection of AD is critically important in view of the growing number of potential new drugs that may influence the course of the disease in its early phases. However, cut-off levels for these CSF biomarkers have not yet been established. Variability in absolute concentrations of AD biomarkers is high among studies and significant differences were noticed even within the same datasets. Variability in biomarkers levels in these assays may be due to many aspects of operating procedures. Standardization of pre-analytical and analytical procedures in collection, treatment, and storage of CSF samples is crucial because differences in sample handling can drastically influence results. Multicenter studies showed that usage of ELISA kits from different manufacturers also affects outcome. So far only very few studies tested the efficiency of ELISA kits produced by different vendors. In this study, the performance of Innogenetics (Gent, Belgium) and Invitrogen (Camarillo, CA, USA) ELISA kits for t-tau and Aβ1–42 was tested. Passing-Bablok analysis showed significant differences between Invitrogen and Innogenetics ELISA methods, making it impossible to use them interchangeably.

Keywords: Alzheimer’s disease; Amyloid β1–42; Biomarkers; Cerebrospinal fluid; ELISA; Standardization; Tau proteins

  • [1] Ferri C.P., Prince M., Brayne C., Brodaty H., Fratiglioni L., Ganguli M., et al., Global prevalence of dementia: a Delphi consensus study, Lancet, 2005, 366, 2112–2117 http://dx.doi.org/10.1016/S0140-6736(05)67889-0CrossrefGoogle Scholar

  • [2] Cummings J.L., Khachaturian Z.S., Definitions and diagnostic criteria, In: Gauthier S. (ed.) Clinical diagnosis and management of Alzheimer’s disease, 2nd ed., Martin Dunitz, London, 2002, 3–13 Google Scholar

  • [3] Wiltfang J., Esselman H., Maler J.M., Bleich S., Huther G., Kornhuber J., Molecular biology of Alzheimer’s dementia and its clinical relevance to early diagnosis and new therapeutic strategies, Gerontology, 2001, 47, 65–71 http://dx.doi.org/10.1159/000052775CrossrefGoogle Scholar

  • [4] Hansson O., Zetterberg H., Buchhave P., Londos E., Blennow K., Minthon L., Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study, Lancet Neurol., 2006, 5, 228–234 http://dx.doi.org/10.1016/S1474-4422(06)70355-6CrossrefGoogle Scholar

  • [5] Mattsson N., Zetterberg H., Hansson O., Andreasen N., Parnetti L., Jonsson M., et al., CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment, J. Am. Med. Assoc., 2009, 302, 385–393 http://dx.doi.org/10.1001/jama.2009.1064CrossrefGoogle Scholar

  • [6] Šimić G., Boban M., Šarac H., Grbić K., Hof P.R., Hamann C., et al., CSF tau proteins in evaluation of patients with suspected dementia, Neurodegen. Dis., 2007, 4, 135–136 http://dx.doi.org/10.1159/000102529CrossrefGoogle Scholar

  • [7] Šimić G., Boban M., Hof P.R., Cerebrospinal fluid phosphorylated tau proteins as predictors of Alzheimer’s disease in subjects with mild cognitive impairment, Period. Biol., 2008, 110, 27–30 Google Scholar

  • [8] Boban M., Grbić K., Mladinov M., Hof P.R., Süβmair C., Ackl N., et al., Cerebrospinal fluid markers in differential diagnosis of Alzheimer’s disease and vascular dementia, Coll. Antropol., 2008, 32, 31–36 Google Scholar

  • [9] Boban M., Šarac H., Mimica N., Mladinov M., Süβmair C., Ackl N., et al., CSF tau proteins in differential diagnosis of dementia, Transl. Neurosci., 2010, 1, 43–48 http://dx.doi.org/10.2478/v10134-010-0013-zCrossrefWeb of ScienceGoogle Scholar

  • [10] Spies P.E., Slats D., Sjögren J.M., Kremer B.P., Verhey F.R., Rikkert M.G., et al., The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer’s disease from non-Alzheimer’s dementia, Curr. Alzheimer Res., 2010, 7, 470–476 http://dx.doi.org/10.2174/156720510791383796CrossrefGoogle Scholar

  • [11] Motter R., Vigo-Pelfrey C., Kholodenko D., Barbour R., Johnson-Wood K., Galasko D., et al., Reduction of β-amyloid peptide 42 in the cerebrospinal fluid of patients with Alzheimer’s disease, Ann. Neurol., 1995, 38, 643–648 http://dx.doi.org/10.1002/ana.410380413CrossrefGoogle Scholar

  • [12] Blennow K., Hampel H., CSF markers for incipient Alzheimer’s disease, Lancet Neurol., 2003, 2, 605–613 http://dx.doi.org/10.1016/S1474-4422(03)00530-1CrossrefGoogle Scholar

  • [13] Sunderland T., Linker G., Mirza N., Putnam K.T., Friedman D.L., Kimmel L.H., et al., Decreased beta-amyloid1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease, J. Am. Med. Assoc., 2003, 289, 2094–2103 http://dx.doi.org/10.1001/jama.289.16.2094CrossrefGoogle Scholar

  • [14] Verwey N.A., van der Flier W.M., Blennow K., Clark C., Sokolow S., De Deyn P.P., et al., A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s disease, Ann. Clin. Biochem., 2009, 46, 235–240 http://dx.doi.org/10.1258/acb.2009.008232CrossrefWeb of ScienceGoogle Scholar

  • [15] Hort J., Bratos A., Pirttila T., Scheltens P., Use of cerebrospinal fluid biomarkers in diagnosis of dementia across Europe, Eur. J. Neurol., 2010, 17, 90–96 http://dx.doi.org/10.1111/j.1468-1331.2009.02753.xCrossrefGoogle Scholar

  • [16] Mattsson N., Andreasson U., Persson S., Arai H., Batish S.D., Bernardini S., et al., The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers, Alzheimers Dement., 2011, 7, 386–395 http://dx.doi.org/10.1016/j.jalz.2011.05.2243CrossrefGoogle Scholar

  • [17] Vanderstichele H., Bibl M., Engelborghs S., Le Bastard N., Lewczuk P., Molinuevo J.L., et al., Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer’s disease diagnosis: a consensus paper from the Alzheimer’s Biomarkers Standardization Initiative, Alzheimers Dement., 2012, 8, 65–73 http://dx.doi.org/10.1016/j.jalz.2011.07.004CrossrefGoogle Scholar

  • [18] Teunissen C.E., Verwey N.A., Kester M.I., van Uffelen K., Blankenstein M.A., Standardization of assay procedures for analysis of the CSF biomarkers amyloid beta (1–42), tau, and phosphorylated tau in Alzheimer’s disease: report of an international workshop, Int. J. Alzheimers Dis., 2010, pii: 635053 Google Scholar

  • [19] Boban M., Malojčić B., Mimica N., Vuković S., Zrilić I., Hof P.R., et al., The reliability and validity of the Mini-Mental State Examination in the elderly Croatian population, Dement. Geriatr. Cogn. Disord., 2012, 33, 385–392 http://dx.doi.org/10.1159/000339596CrossrefWeb of ScienceGoogle Scholar

  • [20] McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M., Clinical diagnosis of Alzheimer’s disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease, Neurology, 1984, 34, 939–944 http://dx.doi.org/10.1212/WNL.34.7.939CrossrefGoogle Scholar

  • [21] Petersen R.C., Smith G.E., Waring S.C., Ivnik R.J., Tangalos E.G., Kokmen E., Mild cognitive impairment: clinical characterization and outcome, Arch. Neurol., 1999, 56, 303–308 http://dx.doi.org/10.1001/archneur.56.3.303CrossrefGoogle Scholar

  • [22] Bablok W., Passing H., Application of statistical procedures in analytical instrument testing, J. Automat. Chem., 1985, 7, 74–79 http://dx.doi.org/10.1155/S1463924685000177CrossrefGoogle Scholar

  • [23] Bilić-Zulle L., Comparison of methods: Passing and Bablok regression, Biochem. Med., 2011, 21, 49–52 http://dx.doi.org/10.11613/BM.2011.010CrossrefGoogle Scholar

  • [24] Mattsson N., Blennow H., Zetterberg H., Inter-laboratory variation in cerebrospinal fluid biomarkers for Alzheimer’s disease: united we stand, divided we fall, Clin. Chem. Lab. Med., 2010, 48, 603–607 http://dx.doi.org/10.1515/cclm.2010.131CrossrefWeb of ScienceGoogle Scholar

  • [25] Verwey N.A., Bouwman F.H., van der Flier W.M., Veerhuis R., Scheltens P., Blankenstein M.A., Variability in longitudinal cerebrospinal fluid tau and phosphorylated tau measurements, Clin. Chem. Lab. Med., 2008, 46, 1300–1304 http://dx.doi.org/10.1515/CCLM.2008.241Web of ScienceCrossrefGoogle Scholar

  • [26] Bjerke M., Portelius E., Minthon L., Wallin A., Anckarsäter H., Anckarsäter R., et al., Confounding factors influencing amyloid beta concentration in cerebrospinal fluid, Int. J. Alzheimers Dis., 2010, pii: 986310 Google Scholar

  • [27] Teunissen C.E., Petzold A., Bennett J.L., Berven F.S., Brundin L., Comabella M., et al., A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking, Neurology, 2009, 73, 1914–1922 http://dx.doi.org/10.1212/WNL.0b013e3181c47cc2Web of ScienceCrossrefGoogle Scholar

  • [28] Fialova L., Bartos A., Svarcova J., Dolezil D., Malbohan I., Stanovení tau proteinu v mozkomíšním moku pacientů s roztroušenou sklerózou dvěma soupravami ELISA [Tau protein determination in cerebrospinal fluid in patients with multiple sclerosis by two ELISA kits], Klin. Biochem. Metab., 2011, 19, 113–118 Google Scholar

  • [29] Regeniter A., Kuhle J., Baumann J., Sollberger M., Herdener M., Kunze U., et al., Biomarkers of dementia: comparison of electrochemiluminescence results and reference ranges with conventional ELISA, Methods, 2012, 56, 494–499 http://dx.doi.org/10.1016/j.ymeth.2012.03.019CrossrefWeb of ScienceGoogle Scholar

  • [30] Olsson A., Vanderstichele H., Andreasen N., De Meyer G., Wallin A., Holmberg B., et al., Simultaneous measurement of β-amyloid(1–42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology, Clin. Chem., 2005, 51, 336–345 http://dx.doi.org/10.1373/clinchem.2004.039347CrossrefGoogle Scholar

  • [31] Reijn T.S., Rikkert M.O., van Geel W.J., de Jong D., Verbeek M.M., Diagnostic accuracy of ELISA and xMAP technology for analysis of amyloid beta (42) and tau proteins, Clin. Chem., 2007, 53, 859–865 http://dx.doi.org/10.1373/clinchem.2006.081679CrossrefGoogle Scholar

  • [32] Fagan A.M., Shaw L.M., Xiong C., Vanderstichele H., Mintun M.A., Trojanowski J.Q., et al., Comparison of analytical platforms for cerebrospinal fluid measures of Aβ1–42, total tau and p-tau181 for identifying Alzheimer’s disease amyloid plaque pathology, Arch. Neurol., 2011, 68, 1137–1144 http://dx.doi.org/10.1001/archneurol.2011.105CrossrefWeb of ScienceGoogle Scholar

  • [33] Wang L.-S., Leung Y.Y., Chang S.-K., Leight S., Knapik-Czajka M., Baek Y., et al., Comparison of xMAP and ELISA assays for detecting cerebrospinal fluid biomarkers of Alzheimer’s disease, J. Alzheimers Dis., 2012, 31, 439–445 Web of ScienceGoogle Scholar

  • [34] Le Bastard N., Coart E., Vanderstichele H., Vanmechelen E., Martin J.J., Engelborghs S., Comparison of two analytical platforms for the clinical qualification of Alzheimer’s disease biomarkers in pathologically-confirmed dementia, J. Alzheimers Dis., 2013, 33, 117–131 Web of ScienceGoogle Scholar

  • [35] Sjögren M., Vanderstichele H., Agren H., Zachrisson O., Edsbagge M., Wikkelsø C., et al., Tau and Abeta42 in cerebrospinal fluid from healthy adults 21–93 years of age: establishment of reference values, Clin. Chem., 2001, 47, 1776–1781 Google Scholar

  • [36] Lewczuk P., Kornhuber J., Vanderstichele H., Vanmechelen E., Esselmann H., Bibl M., et al., Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: a multicenter study, Neurobiol. Aging, 2008, 29, 812–818 http://dx.doi.org/10.1016/j.neurobiolaging.2006.12.010CrossrefWeb of ScienceGoogle Scholar

  • [37] Shaw L.M., Vanderstichele H., Knapik-Czajka M., Figurski M., Coart E., Blennow K., et al., Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI, Acta Neuropathol., 2011, 121, 597–609 http://dx.doi.org/10.1007/s00401-011-0808-0CrossrefWeb of ScienceGoogle Scholar

  • [38] Shaw L.M., Korecka M., Clark C.M., Lee V.M.-Y., Trojanowski J.Q., Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics, Nat. Rev. Drug Discov., 2007, 6, 295–303 http://dx.doi.org/10.1038/nrd2176Web of ScienceCrossrefGoogle Scholar

About the article

Published Online: 2013-06-09

Published in Print: 2013-06-01

Citation Information: Translational Neuroscience, Volume 4, Issue 2, Pages 234–240, ISSN (Online) 2081-6936, ISSN (Print) 2081-3856, DOI: https://doi.org/10.2478/s13380-013-0123-4.

Export Citation

© 2013 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Nicholas Carlin and Sanela Martic-Milne
Journal of The Electrochemical Society, 2018, Volume 165, Number 12, Page G3018
Deepshikha Bhardwaj, Connie Mitra, Chandrakala Aluganti Narasimhulu, Aladdin Riad, Mitsushita Doomra, and Sampath Parthasarathy
Journal of Medicinal Food, 2017
Hei-Nga Chan, Di Xu, See-Lok Ho, Man Shing Wong, and Hung-Wing Li
Chem. Sci., 2017, Volume 8, Number 5, Page 4012
Goran Šimić, Mirjana Babić Leko, Selina Wray, Charles R. Harrington, Ivana Delalle, Nataša Jovanov-Milošević, Danira Bažadona, Luc Buée, Rohan de Silva, Giuseppe Di Giovanni, Claude M. Wischik, and Patrick R. Hof
Progress in Neurobiology, 2017, Volume 151, Page 101
Mirjana Babić Leko, Fran Borovečki, Nenad Dejanović, Patrick R. Hof, Goran Šimić, and Angel Cedazo-Minguez
Journal of Alzheimer's Disease, 2016, Volume 50, Number 3, Page 765

Comments (0)

Please log in or register to comment.
Log in