Original Paper

Acta Neuropathologica

, Volume 117, Issue 3, pp 309-320

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Irina AlafuzoffAffiliated withDepartment of Clinical Medicine, Section of Neuropathology, Unit of Neurology, Kuopio UniversityDepartment of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Email author 
  • , Dietmar R. ThalAffiliated withLaboratory for Neuropathology, Institute of Pathology, University of Ulm
  • , Thomas ArzbergerAffiliated withCentre for Neuropathology and Prion Research, Ludwig-Maximilians-University
  • , Nenad BogdanovicAffiliated withDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet
  • , Safa Al-SarrajAffiliated withDepartment of Clinical Neuropathology, London Institute of Psychiatry
  • , Istvan BodiAffiliated withDepartment of Clinical Neuropathology, London Institute of Psychiatry
  • , Susan BoludaAffiliated withInstitut de Neuropatologia, Universitat de Barcelona
  • , Orso BugianiAffiliated withFondazione Istituto Neurologico Carlo Besta
  • , Charles DuyckaertsAffiliated withLaboratorie Escourolle, Assisstance Publique des Hopitaux de Paris, Universite Pierre et Marie Curie
    • , Ellen GelpiAffiliated withInstitut de Neuropatologia, Universitat de Barcelona
    • , Stephen GentlemanAffiliated withDepartment of Neuropathology, Imperial College
    • , Giorgio GiacconeAffiliated withFondazione Istituto Neurologico Carlo Besta
    • , Manuel GraeberAffiliated withThe Athenaeum
    • , Tibor HortobagyiAffiliated withDepartment of Clinical Neuropathology, London Institute of Psychiatry
    • , Romana HöftbergerAffiliated withInstitute of Neurology, Medical University of Vienna
    • , Paul InceAffiliated withNeuropathology, Royal Hallamshire Hospital
    • , James W. IronsideAffiliated withDepartment of Pathology, Western General Hospital, University of Edinburgh
    • , Nikolaos KavantzasAffiliated withDepartment of Pathology, National and Capodistrian University of Athens
    • , Andrew KingAffiliated withDepartment of Clinical Neuropathology, London Institute of Psychiatry
    • , Penelope KorkolopoulouAffiliated withDepartment of Pathology, National and Capodistrian University of Athens
    • , Gábor G. KovácsAffiliated withInstitute of Neurology, Medical University of Vienna
    • , David MeyronetAffiliated withUniversité Lyon 1 faculté de médecine Laennec, Centre de Neuropathologie et Pathologie Est. Bron Lyon, Hospices Civils de Lyon, Universite de Lyon
    • , Camelia MonoranuAffiliated withPathologisches Institut der Universität Würzburg, Abteilung für Neuropathologie
    • , Tatjana NilssonAffiliated withDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet
    • , Piero ParchiAffiliated withDipartimento di Scienze Neurologiche, Università di Bologna
    • , Efstratios PatsourisAffiliated withDepartment of Pathology, National and Capodistrian University of Athens
    • , Maria PikkarainenAffiliated withDepartment of Clinical Medicine, Section of Neuropathology, Unit of Neurology, Kuopio University
    • , Tamas ReveszAffiliated withQueen Square Brain Bank, UCL Institute of Neurology
    • , Annemieke RozemullerAffiliated withNetherlands Brain Bank
    • , Danielle SeilheanAffiliated withLaboratorie Escourolle, Assisstance Publique des Hopitaux de Paris, Universite Pierre et Marie Curie
    • , Walter Schulz-SchaefferAffiliated withGeorg-August-Universitaet Goettingen
    • , Nathalie StreichenbergerAffiliated withUniversité Lyon 1 faculté de médecine Laennec, Centre de Neuropathologie et Pathologie Est. Bron Lyon, Hospices Civils de Lyon, Universite de Lyon
    • , Stephen B. WhartonAffiliated withNeuroscience Section, University of Sheffield
    • , Hans KretzschmarAffiliated withCentre for Neuropathology and Prion Research, Ludwig-Maximilians-University

Abstract

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.