Assessment of the Pathological Stages of Alzheimer’s Disease in Thin Paraffin Sections: A Comparative Study
Abstract
The staging method proposed by Braak and Braak allows the objective and reliable assessment of Alzheimer-related neurofibrillary pathology. Originally the method was designed for 100-microm thick sections. However, the use of thick sections proved to present difficulties in a routine neuropathology laboratory. In order to adapt the staging method for thin paraffin-embedded sections, we performed an inter- and intrarater study analysing the reliability of the staging method in thin sections. Statistical analysis of the data provided by six independent examiners in two rating sessions reveal kappa values of 0.6-0.8 for both the interrater and the intrarater reliability. The average rate of mistake of the examiners was rarely bigger than a half stage. We conclude that the adapted staging method in thin sections is strongly reliable and we recommend it for staging purposes in institutions where the preparation of thick sections would be difficult.
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CERAD and Braak scoring methods have been shown to have a reasonably high level of reproducibility between observers and among research centers.
“These scoring methods have been shown to have a reasonably high level of reproducibility between observers and among research centers (34-37).”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [36]
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Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Self-citationBancher, C., Jellinger, K., Lassmann, H., Fischer, P., & Leblhuber, F. (1996) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02189115 · Cited by 130 · see citing works
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Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172 · see citing works
Self-citationHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · see citing works
“We recommend continued use of the staging scheme for neurofibrillary degeneration as described originally by Braak and Braak [14, 15], reduced to four stages (Table 2) that improves inter-rater reliability [42].”
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703 · see citing works
Alzheimer’s disease is type 3 diabetes—Evidence reviewed
de la Monte, S. M., & Wands, J. R. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200619 · Cited by 1,158 · see citing works
Beach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31824b211b · Cited by 1,103 · see citing works
Rivera, E. J., Goldin, A., Fulmer, N., Tavares, R., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8304 · Cited by 723 · see citing works
Fernando, M. S., Simpson, J. E., Matthews, F., Brayne, C., Lewis, C. E., Barber, R., Kalaria, R. N., Forster, G., Esteves, F., Wharton, S. B., et al. (2006) · Stroke · doi:10.1161/01.str.0000221308.94473.14 · Cited by 587 · see citing works
Alzheimer's Disease Genetics Consortium, Wetzel-Smith, M. K., Hunkapiller, J., Bhangale, T. R., Srinivasan, K., Maloney, J. A., Atwal, J. K., Sa, S. M., B Yaylaoglu, M., Foreman, O., et al. (2014) · Nature Medicine · doi:10.1038/nm.3736 · Cited by 153 · see citing works
Haddick, P. C. G., Alzheimer’s Disease Genetic Consortium (ADGC), A. D. N. I. (., Larson, J. L., Rathore, N., Bhangale, T. R., Phung, Q. T., Srinivasan, K., Hansen, D. V., Lill, J. R., Pericak-Vance, M. A., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-160524 · Cited by 55 · see citing works
- Authors
- Nagy, Z., Yilmazer-Hanke, D. M., Braak, H., Braak, E., Schultz, C., & Hanke, J.
- Affiliations
- Goethe University Frankfurt (DE)
- ORCID
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 1998
- Volume
- 9
- Issue
- 3
- Pages
- 140-144
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W2005445187
- Cited by
- 51
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Deutsche Forschungsgemeinschaft
- 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, Braak staging, neurofibrillary tangles, neuropathological staging, inter-rater reliability, intra-rater reliability, rating errors, neuropathology
- MeSH terms
- Alzheimer Disease, Brain, Diagnostic Errors, Humans, Microtomy, Observer Variation, Paraffin Embedding
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