Assessment of β-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 Höftberger, Paul Ince, James W. Ironside, Nikolaos Kavantzas, Andrew King, Penelope KorkolopoulouGárbor G. Kovács, 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

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127 Citations (Scopus)


β-Amyloid (Aβ) 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 1 and α synuclein related lesions, also Aβ 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 Aβ, i.e. phase 1 = deposition of Aβ 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 Aβ 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 Aβ-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 Aβ phase in AD is feasible even in large scale retrospective studies.

Original languageEnglish
Pages (from-to)309-320
Number of pages12
JournalActa Neuropathologica
Issue number3
Publication statusPublished - 12 Feb 2009

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