Cited by 122Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer’s disease

Bussire, T, Gold, G, Kvari, E, Giannakopoulos, P, Bouras, C, Perl, D.P, Morrison, J.H, Hof, P.R·2003·Neuroscience

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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Crossref · 10.1016/s0306-4522(02)00942-9

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  • Some, but not all, studies indicate that more neurons disappear in brains of demented subjects than can be explained directly by the number of neurofibrillary tangles and ghost tangles observed at autopsy.

    “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]).”

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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
  • 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, 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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