Inter-laboratory comparison of neuropathological assessments of beta-amyloid protein: a study of the BrainNet Europe consortium.
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.
Alafuzoff
Irina
I
Department of Clinical Medicine, Unit of Neurology, Kuopio University, PO Box 1627, 70 211 Kuopio, Finland. irina.alafuzoff@uku.fi
Pikkarainen
Maria
M
Arzberger
Thomas
T
Thal
Dietmar R
DR
Al-Sarraj
Safa
S
Bell
Jeanne
J
Bodi
Istvan
I
Budka
Herbert
H
Capetillo-Zarate
Estibaliz
E
Ferrer
Isidro
I
Gelpi
Ellen
E
Gentleman
Stephen
S
Giaccone
Giorgio
G
Kavantzas
Nikolaos
N
King
Andrew
A
Korkolopoulou
Penelope
P
Kovács
Gábor G
GG
Meyronet
David
D
Monoranu
Camelia
C
Parchi
Piero
P
Patsouris
Efstratios
E
Roggendorf
Wolfgang
W
Stadelmann
Christine
C
Streichenberger
Nathalie
N
Tagliavini
Fabricio
F
Kretzschmar
Hans
H
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
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016875:tau Proteins