title: Assessment of beta-amyloid deposits in human brain: a study of the BrainNet Europe Consortium.
abstract: 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.
authors.affiliation: Department of Clinical Medicine, Kuopio University, Finland. irina.alafuzoff@uku.fi
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Nenad
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authors.lastname: Bogdanovic
authors.forename: Safa
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authors.lastname: Al-Sarraj
authors.forename: Istvan
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authors.lastname: Bodi
authors.forename: Susan
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authors.lastname: Boluda
authors.forename: Orso
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authors.lastname: Bugiani
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
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: Manuel
authors.initials: M
authors.lastname: Graeber
authors.forename: Tibor
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authors.lastname: Hortobagyi
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.forename: Paul
authors.initials: P
authors.lastname: Ince
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
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: Tatjana
authors.initials: T
authors.lastname: Nilsson
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Maria
authors.initials: M
authors.lastname: Pikkarainen
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Annemieke
authors.initials: A
authors.lastname: Rozemuller
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wharton
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides