Cited by 710Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Evolution of the neuropathology of Alzheimer's disease

Braak, H., Braak, E.·1996·Acta Neurologica Scandinavica

DOI 10.1111/j.1600-0404.1996.tb05866.x

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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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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)
DOI: 10.1111/j.1600-0404.1996.tb05866.x
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
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 7092 d)
Locations: Acta Neurologica Scandinavica (publishedVersion)
PubMed (publishedVersion)
Funders: 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, 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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Evolution of the neuropathology of Alzheimer's disease

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