Assessment of beta-amyloid deposits in human brain: a study of the BrainNet Europe Consortium

Irina Alafuzoff, Dietmar R. Thal, Thomas Arzberger, Nenad Bogdanovic, Safa Al-Sarraj, Istvan Bodi, Susan Boluda, Orso Bugiani, Charles Duyckaerts, Ellen Gelpi, Stephen Gentleman, Giorgio Giaccone, Manuel Graeber, Tibor Hortobagyi, Romana Hoeftberger, Paul Ince, James W. Ironside, Nikolaos Kavantzas, Andrew King, Penelope KorkolopoulouGabor G. Kovacs, David Meyronet, Camelia Monoranu, Tatjana Nilsson, Piero Parchi, Efstratios Patsouris, Maria Pikkarainen, Tamas Revesz, Annemieke Rozemuller, Danielle Seilhean, Walter Schulz-Schaeffer, Nathalie Streichenberger, Stephen B. Wharton, Hans Kretzschmar

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)309-320
Number of pages12
JournalActa Neuropathologica
Volume117
Issue number3
DOIs
Publication statusPublished - Mar 2009

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