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Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry
Open accessAbstract
Assessment of Alzheimer's disease (AD)-related neurofibrillary pathology requires a procedure that permits a sufficient differentiation between initial, intermediate, and late stages. The gradual deposition of a hyperphosphorylated tau protein within select neuronal types in specific nuclei or areas is central to the disease process. The staging of AD-related neurofibrillary pathology originally described in 1991 was performed on unconventionally thick sections (100 mum) using a modern silver technique and reflected the progress of the disease process based chiefly on the topographic expansion of the lesions. To better meet the demands of routine laboratories this procedure is revised here by adapting tissue selection and processing to the needs of paraffin-embedded sections (5-15 mum) and by introducing a robust immunoreaction (AT8) for hyperphosphorylated tau protein that can be processed on an automated basis. It is anticipated that this revised methodological protocol will enable a more uniform application of the staging procedure.
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“Accumulation of Aβ plaques and NFTs follows distinct regional progressions across brain regions as AD advances.”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [14]
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“consistent with the stereotypical hierarchical accumulation of NFTs along neural networks20,21”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [21]
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“They were categorized into the stage C of amyloid deposition and the stage VI of neurofibrillary degeneration, following the Braak's staging (13).”
From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [13]
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“by definition, the primary visual cortex (V1 region) bears NFTs only in Braak NFT stage VI20,21”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [21]
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“we rank ordered the five brain regions based on their known vulnerability to neurofibrillary degeneration20,21 (that is, EC > ITG > PFC > V2 > V1)”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [21]
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“the distinguishing feature between Braak NFT stages V and VI is not just the presence of NFTs in the primary visual (V1), motor and sensory cortical areas, but more severe neurofibrillary degeneration21 and atrophy throughout the cortical mantle51”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [21]
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“A further pathological determinant is loss of neurons, which occurs predominantly in the cortex, the hippocampal formation, and the nucleus basalis of Meynert [2, 3, 18, 22, 25].”
From Transient intraneuronal Aβ rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice (2008) · cites this paper as [2]
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“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 [99]
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Self-citation
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“Hyperphosphorylated tau pathology was determined using the Braak staging method [1, 9, 10].”
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Metadata
- Authors
- Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K.
- Affiliations
- Goethe University Frankfurt (DE)
- Kuopio University Hospital (FI)
- Institut für Neuropathologie (DE)
- Corresponding author
- Braak, Heiko
- Venue
- Acta Neuropathologica
- Published
- 2006-08-12
- Volume
- 112
- Issue
- 4
- Pages
- 389-404
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC3906709
- OpenAlex
- W2093650784
- Cited by
- 3,172
- References
- 101
- Citations by year
- 2026: 218 · 2025: 259 · 2024: 334 · 2023: 254 · 2022: 251 · 2021: 261 · 2020: 228 · 2019: 205 · 2018: 157 · 2017: 135 · 2016: 140 · 2015: 118 · 2014: 134 · 2013: 95 · 2012: 77
- FWCI
- 34.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Neuropathologica (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (LSHM-CT-2004-503039)
- Deutsche Forschungsgemeinschaft
- 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
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neurofibrillary pathology, disease staging, AT8 antibody, immunocytochemistry, paraffin sections, silver staining
- MeSH terms
- Alzheimer Disease, Humans, Immunohistochemistry, Amyloid beta-Peptides, Paraffin Embedding, Tissue Fixation, Neurofibrillary Tangles, tau Proteins, Disease Progression
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