Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium.
It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
Alafuzoff
Irina
I
Department of Neuroscience and Neurology, Kuopio University, Kuopio, Finland. Irina.Alafuzoff@uku.fi
Arzberger
Thomas
T
Al-Sarraj
Safa
S
Bodi
Istvan
I
Bogdanovic
Nenad
N
Braak
Heiko
H
Bugiani
Orso
O
Del-Tredici
Kelly
K
Ferrer
Isidro
I
Gelpi
Ellen
E
Giaccone
Giorgio
G
Graeber
Manuel B
MB
Ince
Paul
P
Kamphorst
Wouter
W
King
Andrew
A
Korkolopoulou
Penelope
P
Kovács
Gábor G
GG
Larionov
Sergey
S
Meyronet
David
D
Monoranu
Camelia
C
Parchi
Piero
P
Patsouris
Efstratios
E
Roggendorf
Wolfgang
W
Seilhean
Danielle
D
Tagliavini
Fabrizio
F
Stadelmann
Christine
C
Streichenberger
Nathalie
N
Thal
Dietmar R
DR
Wharton
Stephen B
SB
Kretzschmar
Hans
H
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D015588:Observer Variation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D013194:Staining and Labeling / Q000379:methods; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D016875:tau Proteins