Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology
Abstract
One histological hallmark in Alzheimer's disease is the tangle. The other is the plaque. A widely discussed hypothesis is the "amyloid cascade" assuming that tangle formation is a direct consequence of amyloid plaque formation. The aim of this study was to examine plaques and tangles in a highly defined neuronal circuitry in order to determine their detailed spatial and temporal relationships. We investigated serial sections of the whole hippocampal formation of brains with early Braak-stages (0-III) for tangles only, i.e. one case at stage 0, six at stage I, six at stage II, and nine at stage III. Most cases displayed both plaques and tangles. Four cases of stages 0 and I, three cases with stage II, and even one with stage III, however, did not display plaques. In turn, no plaque was found in the absence of tangles. The spatial relationship indicates that plaques lay in the terminal fields of tangle-bearing neurons. Our analysis suggests that tangles either antecede plaques or--less likely--are independently formed.
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Neuropathological studies show a differential vulnerability of hippocampal subfields to Alzheimer's disease, with CA1 showing the earliest and strongest changes in neurofibrillary tangles and neuronal loss.
“Interestingly, neuropathological studies have shown a differential vulnerability of hippocampal subfields to AD, with CA1 showing the earliest and strongest changes in terms of both neurofibrillary tangles (NFT) (Braak & Braak, 1991; Schönheit et al., 2004) and neuronal loss (Rössler et al., 2002; West et al., 1994).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Schönheit et al., 2004
The finding of a differential atrophy of the hippocampal subfields in AD, with a stronger and earlier alteration of CA1 and subiculum, is in agreement with neuropathological studies.
“The finding of a differential atrophy of the hippocampal subfields in AD, with a stronger and earlier alteration of CA1 and subiculum, is in agreement with neuropathological studies (Braak & Braak, 1991; Rössler et al., 2002; Schönheit et al., 2004; West et al., 1994).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Schönheit et al., 2004
The higher vulnerability of CA1 neurons is likely to be at least partly due to the neurofibrillary pathology as the CA1 subfield is the first hippocampal area to be affected by NFT.
“The higher vulnerability of CA1 neurons is likely to be at least partly due to the neurofibrillary pathology as the CA1 subfield is the first hippocampal area to be affected by NFT (Braak & Braak, 1991; Schönheit et al., 2004).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Schönheit et al., 2004
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References 51 · Cited by 262
- Authors
- Schönheit, B., Zarski, R., & Ohm, T. G.
- Affiliations
- Stiftung Charité (DE)
- Corresponding author
- Ohm, Thomas G
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 25
- Issue
- 6
- Pages
- 697-711
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2088269376
- Cited by
- 262
- References
- 51
- Citations by year
- 2025: 9 · 2024: 23 · 2023: 12 · 2022: 9 · 2021: 9 · 2020: 17 · 2019: 10 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 14 · 2014: 14 · 2013: 15 · 2012: 13
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (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
- Alzheimer's disease, amyloid plaques, neurofibrillary tangles, amyloid hypothesis, hippocampal formation, Braak stages
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Female, Hippocampus, Humans, Immunohistochemistry, Male, Middle Aged, Temporal Lobe, Neurofibrillary Tangles, Plaque, Amyloid
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