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Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium
Open accessAbstract
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.
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Metadata
- Authors
- Alafuzoff, I., Thal, D. R., Arzberger, T., Bogdanovic, N., Al-Sarraj, S., Bodi, I., Boluda, S., Bugiani, O., Duyckaerts, C., Gelpi, E., Gentleman, S., Giaccone, G., Graeber, M., Hortobagyi, T., Höftberger, R., Ince, P., Ironside, J. W., Kavantzas, N., King, A., Korkolopoulou, P., Kovács, G. G., Meyronet, D., Monoranu, C., Nilsson, T., Parchi, P., Patsouris, E., Pikkarainen, M., Revesz, T., Rozemuller, A., Seilhean, D., Schulz-Schaeffer, W., Streichenberger, N., Wharton, S. B., & Kretzschmar, H.
- Affiliations
- Universität Ulm (DE)
- Institut für Neuropathologie (DE)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Université Pierre-et-Marie-Curie (FR)
- Imperial College London (GB)
- The Athenaeum Club (GB)
- Medical University of Vienna (AT)
- Royal Hallamshire Hospital (GB)
- Western General Hospital (GB)
- National and Kapodistrian University of Athens (GR)
- Lyon 1 Université (FR)
- University of Würzburg (DE)
- Karolinska Institutet (SE)
- University of Bologna (IT)
- University of Sheffield (GB)
- Corresponding author
- Alafuzoff, Irina
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2009-02-01
- Volume
- 117
- Issue
- 3
- Pages
- 309-320
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC2910889
- OpenAlex
- W2138638156
- Cited by
- 193
- References
- 31
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 18 · 2023: 14 · 2022: 13 · 2021: 11 · 2020: 6 · 2019: 17 · 2018: 11 · 2017: 12 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 11 · 2012: 3
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Neuropathologica (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- GRO (submittedVersion, cc-by)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Parkinson's UK (G0909)
- European Commission (LSHM-CT-2004-503039)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- beta-amyloid deposits, Alzheimer's disease, cerebral amyloid angiopathy, interobserver agreement, diencephalon, brainstem, cerebellum, allocortex, neocortex
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Arteries, Female, Humans, Immunohistochemistry, Male, Middle Aged, Reference Values, Reproducibility of Results, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Disease Progression
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