Cited by 838Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Staging of Alzheimer-Related Cortical Destruction

Braak, Heiko, Braak, Eva, Bohl, Jürgen·2008·European Neurology

DOI 10.1159/000116984

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Abstract

The gradual intraneuronal accumulation of an insoluble fibrous material which partly consists of abnormally phosphorylated tau protein (neurofibrillary change) represents an important neuropathological hallmark of Alzheimer’s disease. Neurofibrillary tangles and neuropil threads formed from this material develop in only a few types of cortical pyramidal cells. The first changes are seen in the entorhinal cortex. The destructive process then spreads into the hippocampal formation and eventually encroaches upon the isocortex. This sequence of events permits the distinction of six stages with a progressive increase in the severity of cortical destruction. The entorhinal region serves as an important interface between the isocortex and hippocampus. This interface function is markedly impaired due to the early deterioration of the entorhinal cortex. Severe entorhinal involvement is considered to represent the morphological counterpart of clinically incipient Alzheimer’s disease. Similar changes are found in mentally impaired individuals suffering from Parkinson’s disease or progressive supranuclear palsy.

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“What are the characteristics of the nervous system that are different (see Challenge 2) at the onset [113] of pathological aging? 4.”
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Authors: Braak, H., Braak, E., & Bohl, J.
Affiliations: Goethe University Frankfurt (DE)
ORCID: Braak, Heiko
Venue: European Neurology
Publisher: S. Karger AG
Published: 2008-02-12
Volume: 33
Issue: 6
Pages: 403-408
ISSN: 0014-3022 (ISSN-L)
1421-9913
DOI: 10.1159/000116984
OpenAlex: W2095422335
Cited by: 836
References: 0
Citations by year: 2026: 15 · 2025: 27 · 2024: 29 · 2023: 34 · 2022: 38 · 2021: 32 · 2020: 35 · 2019: 33 · 2018: 30 · 2017: 40 · 2016: 35 · 2015: 47 · 2014: 36 · 2013: 39 · 2012: 35
FWCI: 29.38
Type: journal article
Language: en
Open access: closed
Licence: karger.com/pages/terms-and-conditions (vor)
karger.com/pages/terms-and-conditions (tdm)
Locations: European Neurology (publishedVersion)
PubMed (publishedVersion)
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, cortical destruction, neurofibrillary tangles, tau protein, neuropil threads, entorhinal cortex, hippocampal formation, neocortex, disease staging, cortical pyramidal neurons, Parkinson's disease, progressive supranuclear palsy, neuropathology
MeSH terms: Aged, Alzheimer Disease, Brain Mapping, Cerebral Cortex, Dementia, Diagnosis, Differential, Hippocampus, Humans, Limbic System, Parkinson Disease, Supranuclear Palsy, Progressive, Neurites, Neurofibrillary Tangles

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Staging of Alzheimer-Related Cortical Destruction

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