title: Inter-laboratory comparison of neuropathological assessments of beta-amyloid protein: a study of the BrainNet Europe consortium.
abstract: Amyloid-beta-protein (Abeta) 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 Abeta 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 Abeta-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 Abeta-protein in diagnostics and research. It is noteworthy that to reach reproducible results a dichotomized assessment of Abeta-immunoreactivity rather than quantification and assignment of various types of lesions should be applied, particularly when comparing results obtained by different neuropathologists.
authors.affiliation: Department of Clinical Medicine, Unit of Neurology, Kuopio University, PO Box 1627, 70 211 Kuopio, Finland. irina.alafuzoff@uku.fi
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Maria
authors.initials: M
authors.lastname: Pikkarainen
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Sarraj
authors.forename: Jeanne
authors.initials: J
authors.lastname: Bell
authors.forename: Istvan
authors.initials: I
authors.lastname: Bodi
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Capetillo-Zarate
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Stephen
authors.initials: S
authors.lastname: Gentleman
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Andrew
authors.initials: A
authors.lastname: King
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.forename: David
authors.initials: D
authors.lastname: Meyronet
authors.forename: Camelia
authors.initials: C
authors.lastname: Monoranu
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Roggendorf
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.forename: Fabricio
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D005060:Europe / Q000453:epidemiology; D006801:Humans; D007255:Information Services; D007391:International Cooperation; D016874:Neurofibrillary Tangles / Q000473:pathology; D010446:Peptide Fragments; D058225:Plaque, Amyloid / Q000473:pathology; D040081:Protein Array Analysis / Q000379:methods; D013194:Staining and Labeling; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016875:tau Proteins