Evolution of the neuropathology of Alzheimer's disease
Abstract
Our knowledge of the etiology and pathogenesis of Alzheimer's disease is limited. The most conspicuous changes seen in the brain are deposits of insoluble proteins in both extracellular and intraneuronal locations. The extracellular deposits consist primarily of a specific A4 amyloid protein. The significance of these deposits remains to be determined, as they are often found in the cerebral cortex of non-demented elderly persons. More telling is the gradual accumulation of insoluble fibrous material within some neurons that consists mainly of abnormally phosphorylated tau protein. Six stages of increasingly severe cortical destruction can be distinguished. Stages I and II are characterized by neurofibrillary changes that are largely confined to the transentorhinal region, whereas stages III and IV are marked by severe involvement of both the entorhinal and transentorhinal regions. Isocortical destruction occurs during stages V and VI. This progression in cortical pathology correlates with the gradual worsening of clinical symptoms.
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The hippocampus and associated cortices are affected early in Alzheimer's disease.
“We focused our analysis on the HIC and associated cortices because these structures are known to be affected early in AD26.”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [26]
The hippocampus is not a unitary anatomical formation; several subfields have been identified, differentiable on histological grounds and by functional role in memory encoding and retrieval.
“The hippocampus is not, however, a unitary anatomical formation. Several subfields have been identified, which can be differentiated on both histological grounds [2], [8] and according to their functional role in memory encoding and retrieval [9], [10].”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [2]
Neuropathological changes in AD typically affect the hippocampal formation very early.
“Neuropathological changes in patients with Alzheimer's disease (AD) typically affect the hippocampal formation very early [1], [2].”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [2]
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- Authors
- Braak, H., & Braak, E.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Braak, H.
- ORCID
- Braak, H.
- Venue
- Acta Neurologica Scandinavica
- Publisher
- Wiley
- Published
- 1996-04
- Volume
- 94
- Issue
- S165
- Pages
- 3-12
- ISSN
- 0001-6314 (ISSN-L)
- OpenAlex
- W1971744915
- Cited by
- 710
- References
- 53
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 27 · 2023: 22 · 2022: 29 · 2021: 22 · 2020: 29 · 2019: 27 · 2018: 29 · 2017: 25 · 2016: 31 · 2015: 36 · 2014: 36 · 2013: 31 · 2012: 36
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Neurologica Scandinavica (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, neuropathology, amyloid plaques, tau protein, neurofibrillary tangles, entorhinal cortex, cortical atrophy, disease stage, etiopathogenesis
- MeSH terms
- Alzheimer Disease, Hippocampus, Humans, Neurofibrillary Tangles, Entorhinal Cortex
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