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

  • Alafuzoff, Irina1, 2
  • Thal, Dietmar R.3
  • Arzberger, Thomas4
  • Bogdanovic, Nenad5
  • Al-Sarraj, Safa6
  • Bodi, Istvan6
  • Boluda, Susan7
  • Bugiani, Orso8
  • Duyckaerts, Charles9
  • Gelpi, Ellen7
  • Gentleman, Stephen10
  • Giaccone, Giorgio8
  • Graeber, Manuel11
  • Hortobagyi, Tibor6
  • Höftberger, Romana12
  • Ince, Paul13
  • Ironside, James W.14
  • Kavantzas, Nikolaos15
  • King, Andrew6
  • Korkolopoulou, Penelope15
  • And 14 more
  • 1 Kuopio University, Department of Clinical Medicine, Section of Neuropathology, Unit of Neurology, Kuopio, 70211, Finland , Kuopio (Finland)
  • 2 Uppsala University, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden , Uppsala (Sweden)
  • 3 University of Ulm, Laboratory for Neuropathology, Institute of Pathology, Ulm, Germany , Ulm (Germany)
  • 4 Ludwig-Maximilians-University, Centre for Neuropathology and Prion Research, Munich, Germany , Munich (Germany)
  • 5 Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Huddinge, Sweden , Huddinge (Sweden)
  • 6 London Institute of Psychiatry, Department of Clinical Neuropathology, London, UK , London (United Kingdom)
  • 7 Universitat de Barcelona, Institut de Neuropatologia, Barcelona, Spain , Barcelona (Spain)
  • 8 Fondazione Istituto Neurologico Carlo Besta, Milan, Italy , Milan (Italy)
  • 9 Laboratorie Escourolle, Assisstance Publique des Hopitaux de Paris, Universite Pierre et Marie Curie, Paris, France , Paris (France)
  • 10 Imperial College, Department of Neuropathology, London, UK , London (United Kingdom)
  • 11 The Athenaeum, Pall Mall, London, UK , London (United Kingdom)
  • 12 Medical University of Vienna, Institute of Neurology, Vienna, Austria , Vienna (Austria)
  • 13 Royal Hallamshire Hospital, Neuropathology, Sheffield, UK , Sheffield (United Kingdom)
  • 14 University of Edinburgh, Department of Pathology, Western General Hospital, Edinburgh, UK , Edinburgh (United Kingdom)
  • 15 National and Capodistrian University of Athens, Department of Pathology, Athens, Greece , Athens (Greece)
  • 16 Université Lyon 1 faculté de médecine Laennec, Centre de Neuropathologie et Pathologie Est. Bron Lyon, Hospices Civils de Lyon, Universite de Lyon, Lyon, France , Lyon (France)
  • 17 Pathologisches Institut der Universität Würzburg, Abteilung für Neuropathologie, Würzburg, Germany , Würzburg (Germany)
  • 18 Università di Bologna, Dipartimento di Scienze Neurologiche, Bologna, Italy , Bologna (Italy)
  • 19 UCL Institute of Neurology, Queen Square Brain Bank, London, UK , London (United Kingdom)
  • 20 Netherlands Brain Bank, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 21 Georg-August-Universitaet Goettingen, Göttingen, Germany , Göttingen (Germany)
  • 22 University of Sheffield, Neuroscience Section, Sheffield, UK , Sheffield (United Kingdom)
Published Article
Acta Neuropathologica
Publication Date
Feb 01, 2009
DOI: 10.1007/s00401-009-0485-4
Springer Nature


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 ι 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.

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