Staging of neurofibrillary pathology in Alzheimer's disease: A study of the BrainNet Europe Consortium
Open accessAbstract
It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
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The Braak staging scheme is widely used in neuropathologic criteria for Alzheimer's disease.
“The staging scheme is widely used in neuropathologic criteria for AD [69, 70].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [70]
Most brains from elderly human subjects show abnormalities that fall somewhere along particular continua of pathologic severity.
“We consider it to be an important clue that most brains from elderly human subjects show abnormalities that fall somewhere along particular continua of pathologic severity (60, 96-100).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [96]
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“Hyperphosphorylated tau pathology was determined using the Braak staging method [1, 9, 10].”
MethodHyperphosphorylated Tau in the Occipital Cortex in Aged Nondemented Subjects
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Self-citation
- Authors
- Alafuzoff, I., Arzberger, T., Al‐Sarraj, S., Bodi, I., Bogdanovic, N., Braak, H., Bugiani, O., Del‐Tredici, K., Ferrer, I., Gelpi, E., Giaccone, G., Graeber, M. B., Ince, P., Kamphorst, W., King, A., Korkolopoulou, P., Kovács, G. G., Larionov, S., Meyronet, D., Monoranu, C., Parchi, P., Patsouris, E., Roggendorf, W., Seilhean, D., Tagliavini, F., Stadelmann, C., Streichenberger, N., Thal, D. R., Wharton, S. B., & Kretzschmar, H.
- Affiliations
- Institut für Neuropathologie (DE)
- King's College London (GB)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Hammersmith Hospital (GB)
- University of Sheffield (GB)
- Netherlands Brain Bank (NL)
- National and Kapodistrian University of Athens (GR)
- Országos Pszichiátriai és Neurológiai Intézet (HU)
- University of Bonn (DE)
- Lyon 1 Université (FR)
- University of Würzburg (DE)
- University of Bologna (IT)
- Inserm (FR)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Alafuzoff, Irina
- ORCID
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2008-09-03
- Volume
- 18
- Issue
- 4
- Pages
- 484-496
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC2659377
- OpenAlex
- W2107960095
- Cited by
- 467
- References
- 26
- Citations by year
- 2026: 28 · 2025: 25 · 2024: 50 · 2023: 23 · 2022: 26 · 2021: 31 · 2020: 33 · 2019: 28 · 2018: 27 · 2017: 26 · 2016: 21 · 2015: 19 · 2014: 27 · 2013: 21 · 2012: 16
- FWCI
- 14.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- GRO (submittedVersion, cc-by)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neurofibrillary pathology, hyperphosphorylated tau, neuropil threads, interobserver agreement, immunohistochemistry, regional assessment, molecular classification
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Female, Hippocampus, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, Staining and Labeling, Observer Variation, Neurofibrillary Tangles, tau Proteins, Disease Progression, Neocortex, Plaque, Amyloid
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