Year: 2009
Type: article
Study design: Observational Study
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.
Source: Acta Neuropathologica
Authors: 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 Korkolopoulou, Gábor 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
Institutions: Universität Ulm, Institut für Neuropathologie, Ludwig-Maximilians-Universität München, Karolinska Institutet, Universitat de Barcelona, Fondazione IRCCS Istituto Neurologico Carlo Besta, Université Pierre-et-Marie-Curie, Imperial College London, The Athenaeum Club, Medical University of Vienna, Royal Hallamshire Hospital, Western General Hospital, University of Edinburgh, National and Kapodistrian University of Athens, Lyon 1 Université, Université de Lyon, Hospices Civils de Lyon, University of Würzburg, University of Bologna, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, Netherlands Brain Bank, University of Göttingen, University of Sheffield
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Funders: Parkinson's UK, European Commission
Awards: G3945394334, G8083100563
OpenAlex ID: W2138638156