Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe Consortium.
This interlaboratory study evaluated the reproducibility of the assessments of neuritic plaques and neurofibrillary tangles (NFTs)--the hallmark lesions of Alzheimer disease--and compared the staining between the BrainNet Europe centers. To reduce the topography-related inconsistencies in assessments, we used a 2-mm tissue microarray (TMA) technique. The TMA block included 42 core samples taken from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas silver stains using an immunohistochemical (IHC) method with antibodies directed to beta-amyloid (IHC/Abeta) and hyperphosphorylated tau (IHC/HPtau). The staining quality and the assessments differed between the participants, being most diverse with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas (good/acceptable stain in 57%) and IHC/Abeta (good/acceptable stain in 71%). The most uniform staining quality and assessment was obtained with the IHC/HPtau method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute) that was used significantly influenced the agreement, being highest with NIA-Reagan (54%) recommendations. This agreement was improved by visualization of NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to visualize NFTs and neuropil threads should be considered as a method of choice in a future diagnostic protocol for Alzheimer disease.
Alafuzoff
Irina
I
Department of Neuroscience and Neurology, Kuopio University, Kuopio University Hospital, Finland. irina.alafuzoff@uku.fi
Pikkarainen
Maria
M
Al-Sarraj
Safa
S
Arzberger
Thomas
T
Bell
Jeanne
J
Bodi
Istvan
I
Bogdanovic
Nenad
N
Budka
Herbert
H
Bugiani
Orso
O
Ferrer
Isidro
I
Gelpi
Ellen
E
Giaccone
Giorgio
G
Graeber
Manuel B
MB
Hauw
Jean-Jacques
JJ
Kamphorst
Wouter
W
King
Andrew
A
Kopp
Nicolas
N
Korkolopoulou
Penelope
P
Kovács
Gábor G
GG
Meyronet
David
D
Parchi
Piero
P
Patsouris
Efstratios
E
Preusser
Matthias
M
Ravid
Rivka
R
Roggendorf
Wolfgang
W
Seilhean
Danielle
D
Streichenberger
Nathalie
N
Thal
Dietmar R
DR
Kretzschmar
Hans
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D001706:Biopsy / Q000379:methods / Q000592:standards; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005060:Europe; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards; D007390:International Agencies / Q000592:standards / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D010336:Pathology / Q000379:methods / Q000592:standards; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D012042:Registries / Q000592:standards / Q000706:statistics & numerical data; D016622:Silver Staining / Q000379:methods / Q000592:standards; D013194:Staining and Labeling / Q000379:methods / Q000592:standards*; D014015:Tissue Banks / Q000592:standards / Q000706:statistics & numerical data; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins