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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]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994
(1909) · Cited by 2,575
Buée, L., Bussière, T., Buée‐Scherrer, V., Delacourte, A., & Hof, P. R. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00019-9 · Cited by 2,142
Self-citationProfound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489
Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., & Van Hoesen, G. W. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.1.103 · Cited by 1,380
Life and Death of Neurons in the Aging Brain
Morrison, J. H., & Hof, P. R. (1997) · Science · doi:10.1126/science.278.5337.412 · Cited by 1,344
Self-citationDifferences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease
West, M. J., Coleman, P. D., Flood, D. G., & Troncoso, J. C. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92338-8 · Cited by 1,267
Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen
Economo, C. V., & Koskinas, G. N. (1925) · Springer eBooks · Cited by 1,234
Katzman, R., Terry, R., DeTeresa, R., Brown, T., Davies, P., Fuld, P., Renbing, X., & Peck, A. (1988) · Annals of Neurology · doi:10.1002/ana.410230206 · Cited by 1,225
Unbiased stereological estimation of the number of neurons in the human hippocampus
West, M. J., & Gundersen, H. J. G. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.902960102 · Cited by 1,153
Petrides, M., & Pandya, D. N. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00518.x · Cited by 1,068
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998
Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., & Powell, T. P. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4531 · Cited by 987
Price, J. L., Davis, P. B., Morris, J. C., & White, D. L. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90006-6 · Cited by 818
Some morphometric aspects of the brain in senile dementia of the alzheimer type
Terry, R. D., Peck, A., DeTeresa, R., Schechter, R., & Horoupian, D. S. (1981) · Annals of Neurology · doi:10.1002/ana.410100209 · Cited by 801
Human cingulate cortex: Surface features, flat maps, and cytoarchitecture
Vogt, B. A., Nimchinsky, E. A., Vogt, L. J., & Hof, P. R. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903590310 · Cited by 745
Self-citationClinical Dementia Rating (CDR)
Gauthier, S. G. (2001) · CRC Press eBooks · doi:10.3109/9780203213896-34 · Cited by 696
Neocortical cell counts in normal human adult aging
Terry, R. D., DeTeresa, R. M., & Hansen, L. A. (1987) · Annals of Neurology · doi:10.1002/ana.410210603 · Cited by 686
Identification of normal and pathological aging in prospectively studied nondemented elderly humans
Dickson, D. W., Crystal, H. A., Mattiace, L. A., Masur, D. M., Blau, A. D., Davies, P., Yen, S.-H., & Aronson, M. K. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90027-u · Cited by 643
Regionally specific loss of neurons in the aging human hippocampus
West, M. J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90113-p · Cited by 626
Neuron Number in the Entorhinal Cortex and CA1 in Preclinical Alzheimer Disease
Price, J. L., Ko, A. I., Wade, M. J., Tsou, S. K., McKeel, D. W., & Morris, J. C. (2001) · Archives of Neurology · doi:10.1001/archneur.58.9.1395 · Cited by 596
Crystal, H., Dickson, D., Fuld, P., Masur, D., Scott, R., Mehler, M., Masdeu, J., Kawas, C., Aronson, M., & Wolfson, L. (1988) · Neurology · doi:10.1212/wnl.38.11.1682 · Cited by 586
Lewis, D., Campbell, M., Terry, R., & Morrison, J. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-06-01799.1987 · Cited by 578
Self-citationNeocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease
Bierer, L. M., Hof, P. R., Purohit, D. P., Carlin, L., Schmeidler, J., Davis, K. L., & Perl, D. P. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540250089017 · Cited by 514
Self-citationMemory‐related neural systems in Alzheimer's disease: An anatomic study
Hyman, B. T., Hoesen, G. W. V., & Damasio, A. R. (1990) · Neurology · doi:10.1212/wnl.40.11.1721 · Cited by 449
Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists.
Mirra, S. S., Hart, M. N., & Terry, R. D. (1993) · PubMed · Cited by 412
Rogers, J., & Morrison, J. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-10-02801.1985 · Cited by 410
Self-citationNeurons May Live for Decades with Neurofibrillary Tangles
Morsch, R., Simon, W., & Coleman, P. D. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199902000-00008 · Cited by 370
Campbell, M. J., & Morrison, J. H. (1989) · The Journal of Comparative Neurology · doi:10.1002/cne.902820204 · Cited by 370
Self-citationHof, P. R., Morrison, J. H., & Cox, K. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.903010105 · Cited by 365
Self-citationAuditory cortex on the human posterior superior temporal gyrus
Howard, M. A., Volkov, I. O., Mirsky, R., Garell, P. C., Noh, M. D., Granner, M. A., Damasio, H., Steinschneider, M., Reale, R. A., Hind, J. E., et al. (2000) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(20000103)416:1 · Cited by 335
Self-citationHof, P. R., & Morrison, J. H. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.903010106 · Cited by 294
Self-citationBouras, C., Hof, P. R., Giannakopoulos, P., Michel, J.-P., & Morrison, J. H. (1994) · Cerebral Cortex · doi:10.1093/cercor/4.2.138 · Cited by 280
Self-citationSchmitz, C., & Hof, P. R. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00066-1 · Cited by 272
Self-citationHof, P. R., & Morrison, J. H. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903520202 · Cited by 265
Self-citationJicha, G. A., Lane, E., Vincent, I. J., Ötvös, L., Hoffmann, R., & Davies, P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052087.x · Cited by 264
Kril, J., Patel, S., Harding, A., & Halliday, G. (2002) · Acta Neuropathologica · doi:10.1007/s00401-001-0477-5 · Cited by 190
Sequestration of RNA in Alzheimer's disease neurofibrillary tangles and senile plaques
Ginsberg, S. D., Crino, P. B., Lee, V. M. ‐., Eberwine, J. H., & Trojanowski, J. Q. (1997) · Annals of Neurology · doi:10.1002/ana.410410211 · Cited by 188
Giannakopoulos, P., Hof, P. R., Michel, J., Guimón, J., & Bouras, C. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00023-4 · Cited by 174
Self-citationMorrison, J. H., Lewis, D. A., Campbell, M. J., Huntley, G. W., Benson, D. L., & Bouras, C. (1987) · Brain Research · doi:10.1016/0006-8993(87)90914-0 · Cited by 164
Self-citationBuée‐Scherrer, V., Condamines, O., Mourton-Gilles, C., Jakes, R., Goedert, M., Pau, B., & Delacourte, A. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(96)00003-4 · Cited by 161
Hof, P. R., Nimchinsky, E. A., & Morrison, J. H. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903620107 · Cited by 159
Self-citationHuman orbitofrontal cortex: Cytoarchitecture and quantitative immunohistochemical parcellation
Hof, P. R., Mufson, E. J., & Morrison, J. H. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903590105 · Cited by 157
Self-citationCras, P. P., Smith, M. A., Richey, P. L., Siedlak, S. L., Mulvihill, P., & Perry, G. L. (1995) · Acta Neuropathologica · doi:10.1007/bf00309621 · Cited by 156
Laminar distribution of neocortical senile plaques in senile dementia of the alzheimer type
Duyckaerts, C. J., Hauw, J., Bastenaire, F., Piette, F., Poulain, C., Rainsard, V., Javoy-Agid, F., & Berthaux, P. (1986) · Acta Neuropathologica · doi:10.1007/bf00686079 · Cited by 151
Bouras, C., Hof, P. R., & Morrison, J. H. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90305-5 · Cited by 142
Self-citationRNA sequestration to pathological lesions of neurodegenerative diseases
Ginsberg, S. D., Galvin, J. E., Chiu, T.-L. S., Lee, V. M. ‐., Masliah, E., & Trojanowski, J. Q. (1998) · Acta Neuropathologica · doi:10.1007/s004010050923 · Cited by 142
Vickers, J. C., Riederer, B. M., Marugg, R. A., Buée‐Scherrer, V., Buée, L., Delacourte, A., & Morrison, J. H. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90310-7 · Cited by 133
Self-citationVariation of fractionator estimates and its prediction
Schmitz, C. (1998) · Anatomy and Embryology · doi:10.1007/s004290050191 · Cited by 129
Clinical validity of Braak neuropathological staging in the oldest-old
Gold, G., Bouras, C., Kövari, E., Canuto, A., González Glaría, B., Malky, A., Hof, P. R., Michel, J.-P., & Giannakopoulos, P. (2000) · Acta Neuropathologica · doi:10.1007/s004010051163 · Cited by 128
Self-citationWagner, C. K., & Morrell, J. I. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960617)370:1 · Cited by 127
Variation in hippocampal neuron number with age and brain volume
Harding, A. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.8.710 · Cited by 120
Hof, P. R. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530330070019 · Cited by 118
Self-citationBussière, T., Friend, P. D., Sadeghi, N., Wicinski, B. A., Lin, G. I., Bouras, C., Giannakopoulos, P., Robakis, N. K. R. K., Morrison, J. H., Perl, D. P., et al. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00056-8 · Cited by 108
Self-citationGiannakopoulos, P., Hof, P. R., Mottier, S., Michel, J., & Bouras, C. (1994) · Acta Neuropathologica · doi:10.1007/bf00294172 · Cited by 104
Self-citationProgressive transformation of the cytoskeleton associated with normal aging and Alzheimer's disease
Vickers, J. C., Delacourte, A., & Morrison, J. H. (1992) · Brain Research · doi:10.1016/0006-8993(92)91134-z · Cited by 97
Self-citationHof, P. R., Duan, H., Page, T. L., Einstein, M. C., Wicinski, B. A., He, Y., ERWIN, J. M., & Morrison, J. H. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03345-5 · Cited by 85
Self-citationHof, P. R., Bussière, T., Gold, G., Kövari, E., Giannakopoulos, P., Bouras, C., Perl, D. P., & Morrison, J. H. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.1.55 · Cited by 85
Self-citationNeuroanatomic correlates of visual agnosia in Alzheimer’s disease
Giannakopoulos, P., Gold, G., Duc, M., Michel, J., Hof, P. R., & Bouras, C. (1999) · Neurology · doi:10.1212/wnl.52.1.71 · Cited by 84
Self-citationDynamic regulation of BDNF and NT-3 expression during visual system development
Lein, E. S., Hohn, A., & Shatz, C. J. (2000) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(20000424)420:1 · Cited by 74
Self-citationPractical approaches to stereology in the setting of aging- and disease-related brain banks
Perl, D. P., Good, P. F., Bussière, T., Morrison, J. H., ERWIN, J. M., & Hof, P. R. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00077-6 · Cited by 61
Self-citationDorsolateral Prefrontal Cortex
Binder, M. D., Hirokawa, N., & Windhorst, U. (2008) · Springer eBooks · doi:10.1007/978-3-540-29678-2_1602 · Cited by 53
Lanuza, E., Font, C., Martínez-Marcos, A., & Mart�nez-Garc�a, F. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970811)384:4 · Cited by 50
Self-citationHistometric observations on the metabolism of tangle-bearing neurons
Dayan, A. D., & Ball, M. J. (1973) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(73)90040-3 · Cited by 39
Neurofilament-Immunoreactive Neurons in Alzheimer's Disease and Dementia with Lewy Bodies
Shepherd, C. E., McCann, H., Thiel, E., & Halliday, G. M. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0469 · Cited by 34
Schwab, C., Schulzer, M., Steele, J. C., & McGeer, P. L. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00005-6 · Cited by 24
Diagnostic différentiel histologique de la maladie d'Alzheimer et de la démence sénile
Mutrux, S. (2008) · Monatsschrift für Psychiatrie und Neurologie · doi:10.1159/000148270 · Cited by 23
Giannakopoulos, P., Gold, G., Duc, M., Michel, J., Hof, P. R., & Bouras, C. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017263 · Cited by 22
Self-citationPyramidal neuron loss is matched by ghost tangle increase in Guam parkinsonism-dementia hippocampus
Schwab, C., Steele, J. C., & McGeer, P. L. (1998) · Acta Neuropathologica · doi:10.1007/s004010050912 · Cited by 18
Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons
Martinez-Guijarro, F. J., Briñón, J. G., Blasco-Ib��ez, J. M., Okazaki, K., Hidaka, H., & Alonso, J. R. (1998) · Hippocampus · doi:10.1002/(sici)1098-1063(1998)8:1 · Cited by 11
Binding specificity of monoclonal antibody AD2: influence of the phosphorylation state of tau
Torreilles, F., Roquet, F., Granier, C., Pau, B., & Mourton-Gilles, C. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00073-5 · Cited by 10
Role for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease.
van Geel (2001) · Open Repository and Bibliography (University of Luxembourg) · doi:10.1002/1531-8249(20010201)49:2 · Cited by 7
?imi?, G., Kostovi?, I., Winblad, B., & Bogdanovi?, N. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970324)379:4
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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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