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Cited by 40Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

From the Entorhinal Region via the Prosubiculum to the Dentate Fascia: Alzheimer Disease-Related Neurofibrillary Changes in the Temporal Allocortex

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Braak, Heiko, Del Tredici, Kelly·2020·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nlz123PMC PMC6970449
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Abstract

The pathological process underlying Alzheimer disease (AD) unfolds predominantly in the cerebral cortex with the gradual appearance and regional progression of abnormal tau. Intraneuronal tau pathology progresses from the temporal transentorhinal and entorhinal regions into neocortical fields/areas of the temporal allocortex. Here, based on 95 cases staged for AD-related neurofibrillary changes, we propose an ordered progression of abnormal tau in the temporal allocortex. Initially, abnormal tau was limited to distal dendritic segments followed by tau in cell bodies of projection neurons of the transentorhinal/entorhinal layer pre-α. Next, abnormal distal dendrites accumulated in the prosubiculum and extended into the CA1 stratum oriens and lacunosum. Subsequently, altered dendrites developed in the CA2/CA3 stratum oriens and stratum lacunosum-moleculare, combined with tau-positive thorny excrescences of CA3/CA4 mossy cells. Finally, granule cells of the dentate fascia became involved. Such a progression might recapitulate a sequence of transsynaptic spreading of abnormal tau from 1 projection neuron to the next: From pre-α cells to distal dendrites in the prosubiculum and CA1; then, from CA1 or prosubicular pyramids to CA2 principal cells and CA3/CA4 mossy cells; finally, from CA4 mossy cells to dentate granule cells. The lesions are additive: Those from the previous steps persist.

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  • The vulnerability of entorhinal neurons has been reported in previous studies.

    “The vulnerability of the entorhinal neurons has been reported in many previous studies (Adams et al., 2019, Rodriguez et al., 2019, Braak and Del Tredici, 2020).”

    From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Braak and Del Tredici, 2020

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References 94 · Cited by 40

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Authors
Braak, H., & Del Tredici, K.
Affiliations
  • Universität Ulm (DE)
  • Department of Neurology, Clinical Neuroanatomy, Center for Biomedical Research, University of Ulm From the , Ulm, Germany
Corresponding author
Braak, Heiko
ORCID
Braak, Heiko
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2020-01-08
Volume
79
Issue
2
Pages
163-175
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nlz123
PMC
PMC6970449
OpenAlex
W3000326382
Cited by
40
References
94
Citations by year
2026: 6 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 6
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Hans & Ilse Breuer Foundation
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, tau pathology, dentate gyrus, CA1, mossy cells, dentate gyrus granule cells, projection neurons
MeSH terms
Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Cortex, Dendrites, Female, Humans, Male, Middle Aged, Neurons, Temporal Lobe, Neurofibrillary Tangles, Disease Progression, Entorhinal Cortex, Dentate Gyrus

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