Acta Neuropathologica

, Volume 115, Issue 5, pp 533–546 | Cite as

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

  • Irina Alafuzoff
  • Maria Pikkarainen
  • Thomas Arzberger
  • Dietmar R. Thal
  • Safa Al-Sarraj
  • Jeanne Bell
  • Istvan Bodi
  • Herbert Budka
  • Estibaliz Capetillo-Zarate
  • Isidro Ferrer
  • Ellen Gelpi
  • Stephen Gentleman
  • Giorgio Giaccone
  • Nikolaos Kavantzas
  • Andrew King
  • Penelope Korkolopoulou
  • Gábor G. Kovács
  • David Meyronet
  • Camelia Monoranu
  • Piero Parchi
  • Efstratios Patsouris
  • Wolfgang Roggendorf
  • Christine Stadelmann
  • Nathalie Streichenberger
  • Fabricio Tagliavini
  • Hans Kretzschmar
Original Paper

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.

Keywords

β-Amyloid BrainNet Europe Immunohistochemistry Inter-laboratory study Tissue microarray 

Supplementary material

401_2008_358_MOESM1_ESM.doc (242 kb)
Supplementary tables (DOC 242 kb)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Irina Alafuzoff
    • 1
    • 2
  • Maria Pikkarainen
    • 1
  • Thomas Arzberger
    • 3
  • Dietmar R. Thal
    • 4
  • Safa Al-Sarraj
    • 5
  • Jeanne Bell
    • 6
  • Istvan Bodi
    • 5
  • Herbert Budka
    • 7
  • Estibaliz Capetillo-Zarate
    • 8
  • Isidro Ferrer
    • 9
  • Ellen Gelpi
    • 7
  • Stephen Gentleman
    • 10
  • Giorgio Giaccone
    • 11
  • Nikolaos Kavantzas
    • 12
  • Andrew King
    • 5
  • Penelope Korkolopoulou
    • 12
  • Gábor G. Kovács
    • 7
  • David Meyronet
    • 13
  • Camelia Monoranu
    • 14
  • Piero Parchi
    • 15
  • Efstratios Patsouris
    • 12
  • Wolfgang Roggendorf
    • 14
  • Christine Stadelmann
    • 16
  • Nathalie Streichenberger
    • 13
  • Fabricio Tagliavini
    • 11
  • Hans Kretzschmar
    • 3
  1. 1.Department of Clinical Medicine, Unit of NeurologyKuopio UniversityKuopioFinland
  2. 2.Department of PathologyKuopio University HospitalKuopioFinland
  3. 3.Centre for Neuropathology and Prion ResearchMünchen Ludwig-Maximilians-UniversityMunichGermany
  4. 4.Institute of Pathology, Laboratory of NeuropathologyUniversity of UlmUlmGermany
  5. 5.Department of Clinical NeuropathologyLondon Institute of PsychiatryLondonUK
  6. 6.Department of PathologyEdinburgh University, Western General HospitalEdinburghUK
  7. 7.Institute of NeurologyMedical University of ViennaViennaAustria
  8. 8.Department of NeuropathologyUniversity of BonnBonnGermany
  9. 9.Institut de NeuropathologiaUniversitat de BarcelonaBarcelonaSpain
  10. 10.University Department of NeuropathologyImperial College London and Hammersmith Hospitals TrustLondonUK
  11. 11.Division of Neuropathology and NeurologyInstituto Nazionale Neurologico Carlo BestaMilanItaly
  12. 12.Department of PathologyNational and Capodistrian University of AthensAthensGreece
  13. 13.Centre de Pathologie et de Neuropathologie Est, Hospices Civils de LyonUniversit Lyon 1LyonFrance
  14. 14.Pathologisches Institut, Abteilung Neuropathologieder Universität WürzburgWürzburgGermany
  15. 15.Department of Neurological SciencesUniversity of BolognaBolognaItaly
  16. 16.Department of NeuropathologyGeorg-August-UniversityGöttingenGermany

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