Assessment of beta-amyloid deposits in human brain: a study of the BrainNet Europe Consortium.
beta-Amyloid (A-beta) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as iota and alpha synuclein related lesions, also A-beta related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of A-beta, i.e. phase 1 = deposition of A-beta exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of A-beta phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of A-beta-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer's disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the A-beta phase in AD is feasible even in large scale retrospective studies.
Alafuzoff
Irina
I
Department of Clinical Medicine, Kuopio University, Finland. irina.alafuzoff@uku.fi
Thal
Dietmar R
DR
Arzberger
Thomas
T
Bogdanovic
Nenad
N
Al-Sarraj
Safa
S
Bodi
Istvan
I
Boluda
Susan
S
Bugiani
Orso
O
Duyckaerts
Charles
C
Gelpi
Ellen
E
Gentleman
Stephen
S
Giaccone
Giorgio
G
Graeber
Manuel
M
Hortobagyi
Tibor
T
Höftberger
Romana
R
Ince
Paul
P
Ironside
James W
JW
Kavantzas
Nikolaos
N
King
Andrew
A
Korkolopoulou
Penelope
P
Kovács
Gábor G
GG
Meyronet
David
D
Monoranu
Camelia
C
Nilsson
Tatjana
T
Parchi
Piero
P
Patsouris
Efstratios
E
Pikkarainen
Maria
M
Revesz
Tamas
T
Rozemuller
Annemieke
A
Seilhean
Danielle
D
Schulz-Schaeffer
Walter
W
Streichenberger
Nathalie
N
Wharton
Stephen B
SB
Kretzschmar
Hans
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D015203:Reproducibility of Results
D016229:Amyloid beta-Peptides