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Inter-laboratory comparison of neuropathological assessments of β-amyloid protein: a study of the BrainNet Europe consortium

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Abstract

Amyloid-β-protein (Aβ) is generally assessed by neuropathologists in diagnostics. This BrainNet Europe (http://www.brainnet-europe.org/) (15 centres and 26 participants) study was carried out to investigate the reliability of such an assessment. In the first part of this trial, tissue microarray sections were stained with the antibody of each centre’s choice. Reflecting the reality, seven antibodies and a plethora of pretreatment strategies were used. Ninety-two percent of the stainings were of good/acceptable quality and the estimation of presence of Aβ aggregates yielded good results. However, a poor agreement was reached particularly regarding quantitative (density) and qualitative (diffuse/cored plaques) results. During a joint meeting, the clone 4G8 was determined to label best the fleecy/diffuse plaques, and thus, this clone and the formic acid pretreatment technique were selected for the second part of this study. Subsequently, all stained sections were of good/acceptable quality and again a high level of concordance of the dichotomized (presence/absence) assessment of plaques and CAA was achieved. However, even when only one antibody was used, the type of Aβ-aggregates (diffuse/cored), type of vessel and Vonsattel grade, were not reliably assigned. Furthermore, the quantification of lesions was far from reliable. In line with the first trial, the agreement while assessing density (some, moderate and many) was unimpressive. In conclusion, we can confirm the utility of immunohistochemical detection of Aβ-protein in diagnostics and research. It is noteworthy that to reach reproducible results a dichotomized assessment of Aβ-immunoreactivity rather than quantification and assignment of various types of lesions should be applied, particularly when comparing results obtained by different neuropathologists.

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Acknowledgments

We thank Tarja Kauppinen and all other laboratory technicians of the BNE members for their skilful technical assistance, Ewen MacDonald for critical reading of the manuscript, and Vesa Kiviniemi for his assistance in statistics. We acknowledge the following BNE centres (in alphabetical order of the cities) for contributing the material with generic data used in this study: Netherlands Brain Bank (Amsterdam), National and Capodistrian University of Athens (Athens), Hospital de Bellvitge/Universitat de Barcelona (Barcelona), Alma Mater Studiorum—Università de Bologna (Bologna), National Institute of Psychiatry and Neurology (Budapest, OPNI), The University of Edinburgh (Edinburgh), The Saarland University Hospital (Homburg), University of Kuopio (Kuopio), Imperial College of Science, Technology and Medicine (London), London Institute of Psychiatry (London), Hospices Civils de Lyon (Lyon), Istituto Nazionale Neurologico Carlo Besta (Milan), Ludwig-Maximilians-University of Munich (Munich), Medical University Vienna (Vienna) and University of Wuerzburg (Wuerzburg). This study was supported by European Union grant FP6: BNEII No LSHM-CT-2004-503039. This article reflects only authors’ views and the Community is not liable for any use that may be made of the information contained therein. The study has been authorized by the Ethics Committee of Kuopio University Hospital.

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Authors and Affiliations

  1. Department of Clinical Medicine, Unit of Neurology, Kuopio University, PO Box 1627, 70 211, Kuopio, Finland

    Irina Alafuzoff & Maria Pikkarainen

  2. Department of Pathology, Kuopio University Hospital, Kuopio, Finland

    Irina Alafuzoff

  3. Centre for Neuropathology and Prion Research, München Ludwig-Maximilians-University, Munich, Germany

    Thomas Arzberger & Hans Kretzschmar

  4. Institute of Pathology, Laboratory of Neuropathology, University of Ulm, Ulm, Germany

    Dietmar R. Thal

  5. Department of Clinical Neuropathology, London Institute of Psychiatry, London, UK

    Safa Al-Sarraj, Istvan Bodi & Andrew King

  6. Department of Pathology, Edinburgh University, Western General Hospital, Edinburgh, UK

    Jeanne Bell

  7. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    Herbert Budka, Ellen Gelpi & Gábor G. Kovács

  8. Department of Neuropathology, University of Bonn, Bonn, Germany

    Estibaliz Capetillo-Zarate

  9. Institut de Neuropathologia, Universitat de Barcelona, Barcelona, Spain

    Isidro Ferrer

  10. University Department of Neuropathology, Imperial College London and Hammersmith Hospitals Trust, London, UK

    Stephen Gentleman

  11. Division of Neuropathology and Neurology, Instituto Nazionale Neurologico Carlo Besta, Milan, Italy

    Giorgio Giaccone & Fabricio Tagliavini

  12. Department of Pathology, National and Capodistrian University of Athens, Athens, Greece

    Nikolaos Kavantzas, Penelope Korkolopoulou & Efstratios Patsouris

  13. Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon, Universit Lyon 1, Lyon, France

    David Meyronet & Nathalie Streichenberger

  14. Pathologisches Institut, Abteilung Neuropathologie, der Universität Würzburg, Würzburg, Germany

    Camelia Monoranu & Wolfgang Roggendorf

  15. Department of Neurological Sciences, University of Bologna, Bologna, Italy

    Piero Parchi

  16. Department of Neuropathology, Georg-August-University, Göttingen, Germany

    Christine Stadelmann

Authors
  1. Irina Alafuzoff
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  2. Maria Pikkarainen
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  3. Thomas Arzberger
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  6. Jeanne Bell
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  8. Herbert Budka
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  9. Estibaliz Capetillo-Zarate
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  10. Isidro Ferrer
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  11. Ellen Gelpi
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  14. Nikolaos Kavantzas
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  15. Andrew King
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  16. Penelope Korkolopoulou
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  17. Gábor G. Kovács
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  18. David Meyronet
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  19. Camelia Monoranu
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  20. Piero Parchi
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  21. Efstratios Patsouris
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  22. Wolfgang Roggendorf
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  23. Christine Stadelmann
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  24. Nathalie Streichenberger
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  25. Fabricio Tagliavini
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  26. Hans Kretzschmar
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Corresponding author

Correspondence to Irina Alafuzoff.

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Alafuzoff, I., Pikkarainen, M., Arzberger, T. et al. Inter-laboratory comparison of neuropathological assessments of β-amyloid protein: a study of the BrainNet Europe consortium. Acta Neuropathol 115, 533–546 (2008). https://doi.org/10.1007/s00401-008-0358-2

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  • DOI: https://doi.org/10.1007/s00401-008-0358-2

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