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Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer’s disease
Abstract
Alzheimer's disease (AD) is characterized neuropathologically by several features including extensive neuronal death in the cerebral cortex. In fact, while neuropathological changes restricted to the hippocampal formation are a consistent reflection of age-related memory impairment, overt dementia is present only in cases with neocortical involvement. Several quantitative studies have reported a substantial loss of neurons from these regions and a parallel increase in the number of neurofibrillary tangles (NFT). However, accurate quantitative data on the dynamics of NFT formation are lacking. In the present study, we performed a stereologic analysis of the proportions of intracellular and extracellular (ghost) NFT, and unaffected neurons in the deep part of layer III (layer IIIc) and the superficial part of layer V (layer Va) of Brodmann's prefrontal cortex area 9. Elderly cognitively unimpaired cases were compared with cases with different degrees of cognitive dysfunction. The data revealed differential rates of formation of intracellular and extracellular NFT between the two layers, and confirmed the presence of a severe disease-associated, but not age-related, neuronal loss. It was also shown that a susbtantial number of pyramidal cells may persist either unaffected or in a transitional stage of NFT formation in both neocortical layers. These results suggest that a considerable number of neurons containing an intracellular NFT exists in the neocortex until late in the course of AD. Whereas it is not possible to assess whether such transitional neurons are fully functional, these affected neurons might respond positively to therapeutic strategies aimed at protecting the cells that are prone to neurofibrillary degeneration in AD.
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“Some, but not all, studies have indicated that more neurons disappear in brains of demented subjects than can be explained directly by the number of NFTs and “ghost tangles” observed at autopsy (285, 304, 307-310) (but see [305]).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [309]
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Metadata
- Authors
- Bussire, T., Gold, G., Kvari, E., Giannakopoulos, P., Bouras, C., Perl, D. P., Morrison, J. H., & Hof, P. R.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of Geneva (CH)
- Corresponding author
- Hof, P.R
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 117
- Issue
- 3
- Pages
- 577-592
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2094675227
- Cited by
- 122
- References
- 79
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 2
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, P01AG002219)
- 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, neurofibrillary tangles, neuronal loss, aging, pyramidal neurons, cortical layers, stereology, cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Extracellular Space, Female, Humans, Immunohistochemistry, Male, Neurons, Psychiatric Status Rating Scales, Statistics as Topic, Stereotaxic Techniques, Neurofibrillary Tangles, Prefrontal Cortex, Disease Progression, Capsid Proteins
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