Inter-laboratory comparison of neuropathological assessments of β-amyloid protein: a study of the BrainNet Europe consortium
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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.
Keywordsβ-Amyloid BrainNet Europe Immunohistochemistry Inter-laboratory study Tissue microarray
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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