Cited by 193Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchIntracerebral and Subarachnoid Hemorrhage Research

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

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Alafuzoff, Irina, Thal, Dietmar R., Arzberger, Thomas, Bogdanovic, Nenad, Al-Sarraj, Safa, Bodi, Istvan, Boluda, Susan, Bugiani, Orso, Duyckaerts, Charles, Gelpi, Ellen, Gentleman, Stephen, Giaccone, Giorgio, Graeber, Manuel, Hortobagyi, Tibor, Höftberger, Romana, Ince, Paul, Ironside, James W., Kavantzas, Nikolaos, King, Andrew, Korkolopoulou, Penelope, Kovács, Gábor G., Meyronet, David, Monoranu, Camelia, Nilsson, Tatjana, Parchi, Piero, Patsouris, Efstratios, Pikkarainen, Maria, Revesz, Tamas, Rozemuller, Annemieke, Seilhean, Danielle, Schulz-Schaeffer, Walter, Streichenberger, Nathalie, Wharton, Stephen B., Kretzschmar, Hans·2009·Acta Neuropathologica

DOI 10.1007/s00401-009-0485-4PMC PMC2910889

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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.

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Additional file 3 of Toward a generalizable machine learning workflow for neurodegenerative disease staging with focus on neurofibrillary tangles
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Additional file 3 of Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia
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Additional file 1 of Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia
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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: Alafuzoff, Irina
Thal, Dietmar R.
Arzberger, Thomas
Bugiani, Orso
Duyckaerts, Charles
Giaccone, Giorgio
Höftberger, Romana
Ince, Paul
Ironside, James W.
King, Andrew
Korkolopoulou, Penelope
Kovács, Gábor G.
Meyronet, David
Parchi, Piero
Seilhean, Danielle
Streichenberger, Nathalie
Wharton, Stephen B.
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2009-02-01
Volume: 117
Issue: 3
Pages: 309-320
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-009-0485-4
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: cc-by-nc
creativecommons.org/licenses/by-nc/2.0 (tdm)
creativecommons.org/licenses/by-nc/2.0 (vor)
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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