Cited by 370Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Sequence of Aβ-protein deposition in the human medial temporal lobe

Thal, Dietmar Rudolf, Rüb, Udo, Schultz, Christian, Sassin, Irena, Ghebremedhin, Estifanos, Del Tredici, Kelly, Braak, Eva, Braak, Heiko·2000·Journal of Neuropathology & Experimental Neurology

Abstract

The deposition of Abeta protein (Abeta) and the development of neurofibrillary changes are important histopathological hallmarks of Alzheimer disease (AD). In this study, the medial temporal lobe serves as a model for the changes in the anatomical distribution pattern of different types of Abeta-deposits occurring in the course of AD, as well as for the relationship between the development of Abeta-deposition and that of neurofibrillary pathology. In the first of 4 phases of beta-amyloidosis, diffuse non-neuritic plaques are deposited in the basal temporal neocortex. The same plaque type appears in the second phase within the external entorhinal layers pre-beta and pre-gamma, and fleecy amyloid deposits occur in the internal entorhinal layers pri-alpha, pri-beta, pri-gamma, and in CA1. In the third phase, Abeta-deposits emerge in the molecular layer of the fascia dentata, and band-like Abeta-deposits occur in the subpial portion of the molecular layer of both the entorhinal region and the temporal neocortex. In addition, confluent lake-like Abeta-deposits appear in the parvopyramidal layer of the presubicular region. The fourth phase is characterized by diffuse and core-only plaques in CA4. Diffuse plaques evolve sporadically in the external entorhinal layer pre-alpha. Parallel to the evolution of beta-amyloidosis as represented by the 4 phases, neuritic plaques gradually make their appearance in the temporal neocortex, entorhinal region, CA1, the molecular layer of the fascia dentata, and CA4. A prerequisite for their development is the presence of Abeta and the presence of neurofibrillary tangles in neurons targeting the regions where neuritic plaques evolve. Each of the different types of Abeta-deposits, including neuritic plaques, plays a specific role in the distinct developmental sequence as represented by the 4 phases so that the medial temporal lobe inexorably becomes involved to an ever greater extent. The step-for-step involvement of connected anatomical subfields highlights the importance of the entorhino-hippocampal pathways for the expansion of beta-amyloidosis. The 4 phases in the evolution of beta-amyloidosis correlate significantly with the stages of the neurofibrillary pathology proposed by Braak and Braak.

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Crossref · 10.1093/jnen/59.8.733

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Authors
Thal, D. R., Rüb, U., Schultz, C., Sassin, I., Ghebremedhin, E., Del Tredici, K., Braak, E., & Braak, H.
Affiliations
Goethe University Frankfurt (DE)
Venue
Journal of Neuropathology & Experimental Neurology
Published
2000-08
Volume
59
Issue
8
Pages
733-748
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
OpenAlex
W10604852
Cited by
370
References
52
Citations by year
2026: 14 · 2025: 15 · 2024: 16 · 2023: 15 · 2022: 29 · 2021: 21 · 2020: 26 · 2019: 7 · 2018: 20 · 2017: 8 · 2016: 20 · 2015: 12 · 2014: 8 · 2013: 17 · 2012: 14
FWCI
5.52
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
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
amyloid-beta deposition, Alzheimer's disease, medial temporal lobe, neurofibrillary tangles, neuritic plaques, entorhinal cortex, hippocampus, Braak stages, CA1, CA4, dentate gyrus, temporal neocortex
MeSH terms
Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Neural Pathways, Temporal Lobe, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Neurofibrillary Tangles, Plaque, Amyloid

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