Comparison of four neuropathological scales for Alzheimer’s disease
Abstract
Objective There are several neuropathological scales for staging of Alzheimer pathology. The system proposed by Braak and Braak is based on the topographic distribution of neurofibrillary tangles and neuropil threads, while that of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is based on the quantity of neocortical neuritic plaques. A combination of the Braak and CERAD staging scales was recommended by the National Institute on Aging and Reagan Institute (NIA-RI). The Poly-Pathology Alzheimer's Disease assessment, nine areas (PPAD9) is a staging system based on the extent of neuronal degeneration, microvacuolization, cytoarchitectural disorder and gliosis, in addition to neurofibrillary tangles and neuritic plaques, in nine cerebral regions. The aim of the present study was to critically compare these four neuropathological staging scales. Methods We assessed the Alzheimer pathology, using the four scales, in 43 patients with various dementia disorders, with focus on concordance and differences between the staging systems. Results Comparing the staging systems, the Spearman's rho value for PPAD9 vs. Braak was 0.65, for PPAD9 vs. CERAD 0.72, for PPAD9 vs. NIA-RI 0.67, and for Braak vs. CERAD 0.46. Conclusion The correlation between the neuropathological staging systems was suboptimal, and we conclude that the choice of staging system affects the evaluation of Alzheimer pathology, and hence the final diagnosis.
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Prion-like transcellular propagation of tau pathology may underlie the stereotypical spatiotemporal progression of AD neuropathology described by Braak staging.
“This prion-like transcellular propagation of tau pathology may underlie the stereotypical spatiotemporal progression of AD neuropathology described by Braak staging [46, 47].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [47]
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Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
Hantke, N. C., Kaye, J., Mattek, N., Wu, C.-Y., Dodge, H. H., Beattie, Z., & Woltjer, R. (2023) · PLOS ONE · doi:10.1371/journal.pone.0286812 · Cited by 10 · see citing works
- Authors
- Brunnström, H., & Englund, E.
- Affiliations
- Lund University (SE)
- Venue
- Clinical Neuropathology
- Publisher
- Dustri-Verlgag Dr. Karl Feistle
- Published
- 2011-03-01
- Volume
- 30
- Issue
- 03
- Pages
- 56-69
- ISSN
- 0722-5091 (ISSN-L)
- OpenAlex
- W2066201686
- Cited by
- 17
- References
- 0
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Neuropathology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, Braak staging, CERAD, neurofibrillary tangles, neuritic plaques, dementia diagnosis
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Middle Aged, Pathology, Clinical, Weights and Measures
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