Staging of alzheimer's disease-related neurofibrillary changes
Abstract
Specific immunocytochemical methods (AT8) permit evaluation of neuronal changes well before the actual formation of neurofibrillary tangles and neuropil threads. Initial changes are found in the transentorhinal region (temporal lobe). From here the destructive process encroaches upon the entorhinal region, Ammon's horn, and neocortex. Initial changes occur in comparatively young individuals and can also be observed at the same predilection sites in a few species of old aged domestic animals. In a later state of destruction, AT8 immunoreactive neurons develop typical argyrophilic neurofibrillary tangles and neuropil threads. Six stages of disease propagation can be distinguished with respect to the location of the tangle-bearing neurons and the severity of changes (transentorhinal stages I-II: clinically silent cases; limbic stages III-IV: incipient Alzheimer's disease; neocortical stages V-VI: fully developed Alzheimer's disease). Whole mount techniques reveal the lesional pattern of the particularly severely involved superficial entorhinal layer as seen from the free surface of the parahippocampal gyrus. This approach facilitates recognition of even subtle pathologic changes throughout the entire extent of cortical territories such as the transentorhinal and entorhinal regions.
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Case #1 autopsy showed high degree AD neuropathology per NIA-AA criteria.
“these findings were consistent with a high degree of AD neuropathology per the National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria [3–7].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [3]
Case #3 autopsy revealed high level AD neuropathology per NIA-AA criteria.
“By NIA-AA criteria, the findings met criteria for “high level” AD neuropathology [3–7].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [3]
The cellular pathways that underlie Alzheimer's disease pathological progression across brain regions remain poorly understood.
“but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood1–3.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [1]
Alzheimer's disease is characterized by pathological protein aggregation in a stereotyped pattern across multiple brain regions.
“Alzheimer’s disease (AD) is characterized by pathological protein aggregation in a stereotyped pattern across multiple brain regions1,4.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [1]
Tangles are first seen in the entorhinal cortex (Braak stages I-II), then the hippocampus and thalamus (Braak stages III-IV) and finally the neocortex (Braak stages V-VI), a sequence typically synchronous with cognitive decline from mild cognitive impairment to severe dementia.
“Tangles are first seen in the entorhinal cortex (EC) (Braak stages I–II), then the hippocampus and thalamus (Braak stages III–IV) and finally the neocortex (Braak stages V–VI), a sequence that is typically synchronous with cognitive decline from mild cognitive impairment to severe dementia1,2,4–7.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [1]
Five excitatory neuron subtypes were reduced in patients with AD (vulnerable subtypes) in the early-affected EC and HC, including EC layer II (L2), RORB-positive L5 (AGBL1+GPC5+) and hippocampal CA1 subfield neurons.
“We identified five excitatory neuron subtypes that were reduced in patients with AD (vulnerable subtypes) in the early-affected EC and HC1,17,18, including EC layer II (L2), RORB-positive L5 (AGBL1+GPC5+)19 and hippocampal CA1 subfield neurons20–23.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [1]
The pattern of NFT development across the clinical spectrum of disease has been integrated in Braak neuropathologic staging.
“On the basis of the review of an enormous sample of cross-sectional autopsy data, the pattern of NFT development across the clinical spectrum of disease has been integrated in Braak neuropathologic staging (60, 298, 299).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [298]
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References 46 · Cited by 2,357
- Authors
- Braak, H., & Braak, E.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Braak, Heiko
- ORCID
- Braak, Heiko
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1995-05
- Volume
- 16
- Issue
- 3
- Pages
- 271-278
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2138878035
- Cited by
- 2,357
- References
- 46
- Citations by year
- 2026: 83 · 2025: 93 · 2024: 149 · 2023: 124 · 2022: 131 · 2021: 164 · 2020: 166 · 2019: 113 · 2018: 141 · 2017: 133 · 2016: 115 · 2015: 88 · 2014: 99 · 2013: 78 · 2012: 79
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- 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, neurofibrillary tangles, neuropil threads, disease staging, parahippocampal gyrus, immunocytochemistry, whole-mount pathology, temporal lobe
- MeSH terms
- Alzheimer Disease, Animals, Hippocampus, Humans, Nerve Degeneration, Neurofibrillary Tangles
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