Plaques, tangles and dementia
Abstract
We have made a histological study of the cerebral cortex and hippocampus from 59 consecutively autopsied subjects, aged 51-102 years, prospectively assessed for the presence and extent (or absence) of dementia. Counts were obtained of the numbers of argyrophilic plaques and neurofibrillary tangles in each area examined. In demented patients without evidence of cerebrovascular disease, a highly significant correlation was found between the presence and severity of dementia and the number of neurofibrillary tangles in the cerebral cortex. A significant but much weaker and inconstant correlation was obtained between the presence and severity of dementia and the number of argyrophilic plaques present in the cortex. The temporal lobe cortex and hippocampus were the areas most severely affected by the increased neurofibrillary tangle formation in senile dementia due to Alzheimer's disease.
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Previous studies helped establish the connection between amyloid-beta plaques, neurofibrillary tangles, and antemortem cognitive impairment.
“and previous studies that had also helped to establish the connection between AβPs, NFTs, and antemortem cognitive impairment (311-320).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [319]
Cites
Blessed, G., Tomlinson, B. E., & Roth, M. (1968) · British Journal of Psychiatry · doi:10.1192/bjp.114.512.797 · Cited by 4,117 · see citing works
Observations on the brains of demented old people
Tomlinson, B. E., Blessed, G., & Roth, M. (1970) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(70)90063-8 · Cited by 2,084 · see citing works
Perry, E., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P., & Perry, R. H. (1978) · British medical journal · doi:10.1136/bmj.2.6150.1457 · Cited by 2,043 · see citing works
EVALUATION OF A MENTAL TEST SCORE FOR ASSESSMENT OF MENTAL IMPAIRMENT IN THE ELDERLY
HODKINSON, H. M. (1972) · Age and Ageing · doi:10.1093/ageing/1.4.233 · Cited by 1,695 · see citing works
Uber eine eigenartige Erkrankung der Hirnrinde
Alzheimer, A. (1907) · Medical Entomology and Zoology · Cited by 1,503 · see citing works
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 · see citing works
Observations on the brains of non-demented old people
Tomlinson, B. E., Blessed, G., & Roth, M. (1968) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(68)90154-8 · Cited by 681 · see citing works
Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading
Brun, A., & Englund, E. M. (1981) · Histopathology · doi:10.1111/j.1365-2559.1981.tb01818.x · Cited by 559 · see citing works
Organic Psychiatry: The Psychological Consequences of Cerebral Disorder
Lishman, W. (1978) · Cited by 483 · see citing works
Alzheimer's Neurofibrillary Changes: A Topographic Study
HIRANO, A. (1962) · Archives of Neurology · doi:10.1001/archneur.1962.04210030065009 · Cited by 402 · see citing works
ROTH, M., TOMLINSON, B. E., & BLESSED, G. (1966) · Nature · doi:10.1038/209109a0 · Cited by 298 · see citing works
Ball, M. J. (1978) · Acta Neuropathologica · doi:10.1007/bf00690970 · Cited by 251 · see citing works
Die Krampfschädigungen des Gehirns
Scholz, W. (1951) · Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie · doi:10.1007/978-3-642-86299-1 · Cited by 214 · see citing works
The limbic system in Alzheimer's disease. A neuropathologic investigation.
Hopper, M., & Vogel, F. S. (1976) · PubMed Central · Cited by 208 · see citing works
Dayan, A. D. (1970) · Acta Neuropathologica · doi:10.1007/bf00687663 · Cited by 176 · see citing works
Organic Psychiatry The Psychological Consequences of Cerebral Disorder
Durward, W. F. (1979) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.42.8.772-a · Cited by 168 · see citing works
THE DENSITY OF NEURONS IN THE HUMAN HIPPOCAMPUS
Dam, A. M. (1979) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1979.tb00624.x · Cited by 136 · see citing works
Dayan, A. D. (1970) · Acta Neuropathologica · doi:10.1007/bf00687664 · Cited by 105 · see citing works
MENTAL ILLNESS AND THE AGEING BRAIN
Cumings, J. N. (1963) · Journal of Clinical Pathology · doi:10.1136/jcp.16.1.98-c · Cited by 93 · see citing works
NEUROFIBRILLARY TANGLES AND THE PATHOGENESIS OF DEMENTIA: A QUANTITATIVE STUDY
Ball, M. J. (1976) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1976.tb00513.x · Cited by 87 · see citing works
Senile Degenerative Brain Lesions and Dementia
Morimatsu, M., Hirai, S., Muramatsu, A., & Yoshikawa, M. (1975) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1975.tb00425.x · Cited by 86 · see citing works
Alzheimer's Disease and Related Conditions
Daniel, P. M. (1971) · Journal of Clinical Pathology · doi:10.1136/jcp.24.4.373-c · Cited by 83 · see citing works
Rb, C. (1982) · PubMed · Cited by 74 · see citing works
Clinical check list for diagnosis of dementia.
Hare, M. (1978) · BMJ · doi:10.1136/bmj.2.6132.266 · Cited by 51 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134 · see citing works
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · see citing works
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984) · Science · doi:10.1126/science.6474172 · Cited by 2,268 · see citing works
The cholinergic hypothesis of Alzheimer’s disease: A review of progress
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.66.2.137 · Cited by 2,198 · see citing works
Self-citationThe spectrum of disease in chronic traumatic encephalopathy
McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H.-S., Hall, G., Wojtowicz, S. M., Baugh, C. M., et al. (2013) · Brain · doi:10.1093/brain/aws307 · Cited by 2,098 · see citing works
Cryo-EM structures of tau filaments from Alzheimer’s disease
Fitzpatrick, A. W. P., Falcon, B., He, S., Murzin, A. G., Murshudov, G., Garringer, H. J., Crowther, R. A., Ghetti, B., Goedert, M., & Scheres, S. H. W. (2017) · Nature · doi:10.1038/nature23002 · Cited by 2,061 · see citing works
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
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 · see citing works
Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease
Mori, H., Kondo, J., & Ihara, Y. (1987) · Science · doi:10.1126/science.3029875 · Cited by 843 · see citing works
Neuron numbers and dendritic extent in normal aging and Alzheimer’s disease
Coleman, P. D., & Flood, D. G. (1987) · Neurobiology of Aging · doi:10.1016/0197-4580(87)90127-8 · Cited by 772 · see citing works
Perforant pathway changes and the memory impairment of Alzheimer's disease
Hyman, B. T., Van Hoesen, G. W., Kromer, L. J., & Damasio, A. R. (1986) · Annals of Neurology · doi:10.1002/ana.410200406 · Cited by 672 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
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 · see citing works
Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles
Guo, J. L., & Lee, V. M.-Y. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209296 · Cited by 636 · see citing works
Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders
Jucker, M., & Walker, L. C. (2011) · Annals of Neurology · doi:10.1002/ana.22615 · Cited by 622 · see citing works
“Whereas the degree of tauopathy correlates strongly with cognitive decline in AD 6-8 , genetic, pathologic and biochemical evidence implicates the aggregation of A β as a critical, early trigger in the chain of events that leads to tauopathy, neuronal dysfunction and dementia 9 .”
BackgroundLewis, D., Campbell, M., Terry, R., & Morrison, J. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-06-01799.1987 · Cited by 578 · see citing works
Wilcock, G. K., Esiri, M. M., Bowen, D. M., & Smith, C. C. T. (1982) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(82)90045-4 · Cited by 553 · see citing works
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 · see citing works
Irizarry, M. C., Soriano, F., McNamara, M., Page, K. J., Schenk, D., Games, D., & Hyman, B. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-18-07053.1997 · Cited by 497 · see citing works
Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies
Brunden, K. R., Trojanowski, J. Q., & Lee, V. M.-Y. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2959 · Cited by 440 · see citing works
Correlations of synaptic and pathological markers with cognition of the elderly
Dickson, D. W., Crystal, H. A., Bevona, C., Honer, W., Vincent, I., & Davies, P. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00013-5 · Cited by 410 · see citing works
Zhang, B., Carroll, J., Trojanowski, J. Q., Yao, Y., Iba, M., Potuzak, J. S., Hogan, A.-M. L., Xie, S. X., Ballatore, C., Smith, A. B., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4922-11.2012 · Cited by 401 · see citing works
Hof, P. R., Morrison, J. H., & Cox, K. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.903010105 · Cited by 365 · see citing works
Neuritic pathology and dementia in alzheimer's disease
McKee, A. C., Kosik, K. S., & Kowall, N. W. (1991) · Annals of Neurology · doi:10.1002/ana.410300206 · Cited by 358 · see citing works
Validation of clinical diagnostic criteria for Alzheimer's disease
Morris, J. C., McKeel, D. W., Fulling, K., Torack, R. M., & Berg, L. (1988) · Annals of Neurology · doi:10.1002/ana.410240105 · Cited by 362 · see citing works
Harada, R., Okamura, N., Furumoto, S., Furukawa, K., Ishiki, A., Tomita, N., Tago, T., Hiraoka, K., Watanuki, S., Shidahara, M., et al. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.164848 · Cited by 330 · see citing works
Cummings, B. J., Pike, C. J., Shankle, R., & Cotman, C. W. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00170-4 · Cited by 305 · see citing works
Haroutunian, V. (1998) · Archives of Neurology · doi:10.1001/archneur.55.9.1185 · Cited by 289 · see citing works
Bouras, 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 · see citing works
Chan‐Palay, V. (1987) · Journal of Comparative Neurology · doi:10.1002/cne.902600205 · Cited by 254 · see citing works
Takeuchi, A., Irizarry, M. C., Duff, K., Saido, T. C., Hsiao Ashe, K., Hasegawa, M., Mann, D. M. A., Hyman, B. T., & Iwatsubo, T. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64544-0 · Cited by 229 · see citing works
Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer’s disease
de la Monte, S. M. (1989) · Annals of Neurology · doi:10.1002/ana.410250506 · Cited by 229 · see citing works
Iba, M., McBride, J. D., Guo, J. L., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1458-4 · Cited by 223 · see citing works
Goedert, M., & Spillantini, M. G. (2017) · Molecular Brain · doi:10.1186/s13041-017-0298-7 · Cited by 213 · see citing works
Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease
Haroutunian, V., Purohit, D. P., Perl, D. P., Marin, D., Khan, K., Lantz, M., Davis, K. L., & Mohs, R. C. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.713 · Cited by 201 · see citing works
Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment
Andrade, S., Ramalho, M. J., Pereira, M. D. C., & Loureiro, J. A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01261 · Cited by 173 · see citing works
Nonhuman Primate Models of Alzheimer-Like Cerebral Proteopathy
Heuer, E., F. Rosen, R., Cintron, A., & C. Walker, L. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799315885 · Cited by 169 · see citing works
Modeling the Relation Between Neurofibrillary Tangles and Intellectual Status
Duyckaerts, C. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)80306-5 · Cited by 150 · see citing works
Tauopathy with paired helical filaments in an aged chimpanzee
Rosen, R. F., Farberg, A. S., Gearing, M., Dooyema, J., M. Long, P., Anderson, D. C., Davis‐Turak, J., Coppola, G., Geschwind, D. H., Paré, J., et al. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21744 · Cited by 153 · see citing works
Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation
Crowe, A., James, M. J., Lee, V. M.-Y., Smith, A. B., Trojanowski, J. Q., Ballatore, C., & Brunden, K. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.436006 · Cited by 143 · see citing works
Communication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome
Contestabile, A., Benfenati, F., & Gasparini, L. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.003 · Cited by 134 · see citing works
Bancher, C., Jellinger, K., Lassmann, H., Fischer, P., & Leblhuber, F. (1996) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02189115 · Cited by 130 · see citing works
Mann, D. M. A., Yates, P. O., & Marcyniuk, B. (1985) · Neuroscience Letters · doi:10.1016/0304-3940(85)90439-2 · Cited by 127 · see citing works
Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets
Lee, V. M.-Y., Brunden, K. R., Hutton, M., & Trojanowski, J. Q. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006437 · Cited by 122 · see citing works
Immunotherapy Targeting Pathological Tau Protein in Alzheimer's Disease and Related Tauopathies
Sigurdsson, E. M. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-15202 · Cited by 116 · see citing works
Welikovitch, L. A., Do Carmo, S., Maglóczky, Z., Malcolm, J. C., Lőke, J., Klein, W. L., Freund, T., & Cuello, A. C. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914593117 · Cited by 116 · see citing works
Duyckaerts, C., Brion, J. P., Hauw, J. J., & Flament-Durand, J. (1987) · Acta Neuropathologica · doi:10.1007/bf00693783 · Cited by 89 · see citing works
MANN, D. M. A., TUCKER, C. M., & YATES, P. O. (1987) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1987.tb00176.x · Cited by 80 · see citing works
Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer's disease
Bennett, D. A., Cochran, E. J., Saper, C. B., Leverenz, J. B., Gilley, D. W., & Wilson, R. S. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90043-b · Cited by 67 · see citing works
Duyckaerts, C., Delaère, P., Poulain, V., Brion, J.-P., & Hauw, J.-J. (1988) · Neuroscience Letters · doi:10.1016/0304-3940(88)90706-9 · Cited by 65 · see citing works
Mechanisms of cell death in Alzheimer’s disease
Bancher, C., Lassmann, H., Breitschopf, H., & Jellinger, K. A. (1997) · Journal of Neural Transmission. Supplementa · doi:10.1007/978-3-7091-6842-4_14 · Cited by 50 · see citing works
- Authors
- Wilcock, G. K., & Esiri, M. M.
- Affiliations
- John Radcliffe Hospital (GB)
- University of Oxford (GB)
- Corresponding author
- Wilcock, G.K.
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 1982-11
- Volume
- 56
- Issue
- 2-3
- Pages
- 343-356
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W1569576869
- Cited by
- 608
- References
- 24
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 17 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 20 · 2019: 10 · 2018: 19 · 2017: 8 · 2016: 18 · 2015: 6 · 2014: 9 · 2013: 12 · 2012: 12
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the Neurological Sciences (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, senile dementia, neurofibrillary tangles, cerebral cortex, hippocampus, temporal lobe, dementia severity, neuropathology
- MeSH terms
- Aged, Alzheimer Disease, Cerebral Cortex, Cerebrovascular Disorders, Dementia, Hippocampus, Humans, Middle Aged, Neurofibrils
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