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

Mirjana Babić 1 , Željka Vogrinc 2 , Andrea Diana 3 , Nataša Klepac 4 , Fran Borovečki 4 , Patrick Hof 5 ,  and Goran Šimić 1
  • 1 Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Šalata 12, 10000, Zagreb, Croatia
  • 2 Laboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia
  • 3 Laboratory of Neurogenesis and Neuropoiesis, Department of Biomedical Sciences, University of Cagliari, Città Universitaria di Monserrato, 09042, Monserrato (Cagliari), Italy
  • 4 Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb Medical School, University Hospital Center Zagreb, Šalata 2, 10000, Zagreb, Croatia
  • 5 Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

Abstract

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.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • [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)67889-0

  • [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

  • [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/10.1159/000052775

  • [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)70355-6

  • [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.2009.1064

  • [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/10.1159/000102529

  • [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

  • [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

  • [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-z

  • [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/10.2174/156720510791383796

  • [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.410380413

  • [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)00530-1

  • [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.289.16.2094

  • [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.2009.008232

  • [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.x

  • [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.2011.05.2243

  • [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.2011.07.004

  • [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

  • [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/10.1159/000339596

  • [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.34.7.939

  • [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.56.3.303

  • [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/S1463924685000177

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

  • [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.2010.131

  • [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.2008.241

  • [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

  • [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.0b013e3181c47cc2

  • [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

  • [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.2012.03.019

  • [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.2004.039347

  • [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.2006.081679

  • [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.2011.105

  • [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

  • [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

  • [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

  • [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.2006.12.010

  • [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/s00401-011-0808-0

  • [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/nrd2176

OPEN ACCESS

Journal + Issues

Translational Neuroscience provides a closer interaction between basic and clinical neuroscientists to expand understanding of brain structure, function and disease, and translate this knowledge into clinical applications and novel therapies of nervous system disorders.
Reports novel findings that are likely to change the direction of thinking and practice in biomedical sciences. Covers research findings in all subfields of neuroscience.

Search