Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Abstract
We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer's disease patients who had been examined during life. We counted NFTs and SPs in 13 cytoarchitectural regions representing limbic, primary sensory, and association cortices, and in subcortical neurotransmitter-specific areas. The degree of neuropathologic change was compared with the severity of dementia, as assessed by the Blessed Dementia Scale and duration of illness. We found that (1) the severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition; (2) NFTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields; (3) NFTs appeared in the entorhinal cortex, CA1/subiculum field of the hippocampal formation, and the amygdala early in the disease process; and (4) the degree of SP deposition was also related to a hierarchic vulnerability of certain brain areas to accumulate SPs, but the pattern of SP distribution was different from that of NFT.
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Studies have shown that the number and location of neurofibrillary tangles correlates with neuronal loss, disease severity and clinical course.
“Studies have shown that their number and location correlates with neuronal loss, disease severity and clinical course [65, 66].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [66]
Neurofibrillary tangles and quantitative neuronal loss, but not amyloid plaques, correlate with disease severity and dementia duration.
“Neurofibrillary tangles and quantitative neuronal loss, but not amyloid plaques, have been found to correlate with disease severity and dementia duration [21–23].”
From Clinical trials of new drugs for Alzheimer disease (2020) · cites this paper as [22]
Hyperphosphorylated tau correlates with measures of cognitive decline in humans.
“to correlate with measures of cognitive decline (Arriagada et al., 1992) in humans.”
From Network analysis identifies strain-dependent response to tau and tau seeding-associated genes (2023) · cites this paper as Arriagada et al., 1992
In Alzheimer's disease patients, the clinical severity of dementia strongly correlates with the load of pathological tau aggregates.
“In AD patients, the clinical severity of dementia strongly correlates with the load of pathological tau aggregates. 3 , 4”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [3]
Correlations between NFT density and clinical symptoms such as cognitive decline in AD have been demonstrated.
“Correlations between NFT density and clinical symptoms, such as a cognitive decline in AD, have been demonstrated [11, 12].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [11]
Increasing evidence demonstrates that cognitive dysfunction and disease severity are more related to tau pathology.
“Increasing evidence demonstrates that the cognitive dysfunction and severity of the disease are more related to tau pathology [11–14].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [11]
Tau pathology is more associated with cognitive dysfunction than Aβ pathology, making tau a potential therapeutic target.
“Tau has received increasing attention as a potential therapeutic target, since evidence indicates that tau pathology is more associated with cognitive dysfunction.”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [11]
NFTs and quantitative neuronal loss may be more closely correlated with disease severity and dementia progression than the amyloid plaque burden.
“NFTs and quantitative neuronal loss may be more closely correlated with disease severity and dementia progression than the amyloid plaque burden [20–22].”
From Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update (2023) · cites this paper as [21]
The best pathological correlate for clinical symptoms to date is the extent of neurofibrillary tangle formation.
“the best pathological correlate for clinical symptoms to date is the extent of NFT formation (Arriagada et al., 1992; Brier et al., 2016; Giannakopoulos et al., 2003)”
From Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis (2020) · cites this paper as Arriagada et al., 1992
There is a strong link between neocortical NFTs and cognitive decline.
“a large number of studies have arrived at a common finding, namely, there is a strong link between neocortical NFTs and cognitive decline (Tomlinson et al., 1970; Duyckaerts et al., 1990, 1997, 1998; Mckee et al., 1991; Arriagada et al., 1992;”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Arriagada et al., 1992
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Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329 · see citing works
“Studies have shown that their number and location correlates with neuronal loss, disease severity and clinical course [65, 66].”
BackgroundNeuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345 · see citing works
Self-citationBraak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172 · 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
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
The 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
Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014 · see citing works
Self-citationNelson, 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
“These inclusion criteria do not minimize the contributions of studies with smaller sample sizes, for example, the important CPC study by Arriagada et al (293) that assessed 10 patients.”
BackgroundSelf-citationTau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · see citing works
Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925 · see citing works
Adult-derived neural precursors transplanted into multiple regions in the adult brain
Herrera, D. G., García‐Verdugo, J. M., & Álvarez-Buylla, A. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199912)46:6 · Cited by 204 · see citing works
Profound 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 · see citing works
“…cases also occur in the CA1–subiculum of the hippocampus, the perirhinal cortex, inferior temporal gyrus, the amygdala and posterior parahippocampal gyri, cholinergic basal forebrain, and dorsal raphe, although in general to a less dramatic extent than layer II of the EC (Arriagada et al., 1992a).”
BackgroundInfluentialSelf-citationNeuronal 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
Self-citationMutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474 · see citing works
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment
Jack, C. R., Petersen, R. C., Xu, Y. C., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Waring, S. C., Tangalos, E. G., & Kokmen, E. (1999) · Neurology · doi:10.1212/wnl.52.7.1397 · Cited by 1,404 · see citing works
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 · see citing works
Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells
Israel, M. A., Yuan, S. H., Bardy, C., Reyna, S. M., Mu, Y., Herrera, C., Hefferan, M. P., Van Gorp, S., Nazor, K. L., Boscolo, F. S., et al. (2012) · Nature · doi:10.1038/nature10821 · Cited by 1,253 · see citing works
Billings, L. M., Oddo, S., Green, K. N., McGaugh, J. L., & LaFerla, F. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.040 · Cited by 1,294 · see citing works
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · see citing works
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Näslund, J. (2000) · JAMA · doi:10.1001/jama.283.12.1571 · Cited by 1,268 · see citing works
Synergy between amyloid-β and tau in Alzheimer’s disease
Busche, M. A., & Hyman, B. T. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0687-6 · Cited by 1,242 · see citing works
Self-citationApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220 · see citing works
PET Imaging of Tau Deposition in the Aging Human Brain
Schöll, M., Lockhart, S. N., Schonhaut, D. R., O’Neil, J. P., Janabi, M., Ossenkoppele, R., Baker, S. L., Vogel, J. W., Faria, J., Schwimmer, H. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.028 · Cited by 1,214 · see citing works
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease
Ossenkoppele, R., Schonhaut, D. R., Schöll, M., Lockhart, S. N., Ayakta, N., Baker, S. L., O’Neil, J. P., Janabi, M., Lazaris, A., Cantwell, A., et al. (2016) · Brain · doi:10.1093/brain/aww027 · Cited by 1,185 · see citing works
Dickerson, B. C., Bakkour, A., Salat, D. H., Feczko, E., Pacheco, J., Greve, D. N., Grodstein, F., Wright, C. I., Blacker, D., Rosas, H. D., et al. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn113 · Cited by 1,153 · see citing works
Self-citationDynamics of Gray Matter Loss in Alzheimer's Disease
Thompson, P. M., Hayashi, K. M., de Zubicaray, G., Janke, A. L., Rose, S. E., Semple, J., Herman, D., Hong, M. S., Dittmer, S. S., Doddrell, D. M., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00994.2003 · Cited by 1,132 · see citing works
Tau in Alzheimer Disease and Related Tauopathies
Iqbal, K., Liu, F., Gong, C., & Grundke, I. (2010) · Current Alzheimer Research · doi:10.2174/156720510793611592 · Cited by 1,122 · see citing works
Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
Giannakopoulos, P., Herrmann, F. R., Bussière, T., Bouras, C., Kövari, E., Perl, D. P., Morrison, J. H., Gold, G., & Hof, P. R. (2003) · Neurology · doi:10.1212/01.wnl.0000063311.58879.01 · Cited by 1,118 · see citing works
Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107 · see citing works
Self-citationTau pathology in Alzheimer disease and other tauopathies
Iqbal, K., del C. Alonso, A., Chen, S., Chohan, M. O., El-Akkad, E., Gong, C.-X., Khatoon, S., Li, B., Liu, F., Rahman, A., et al. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.09.008 · Cited by 1,037 · see citing works
Role of tau protein in both physiological and pathological conditions
AVILA, J., LUCAS, J. J., PÉREZ, M., & HERNÁNDEZ, F. (2004) · Physiological Reviews · doi:10.1152/physrev.00024.2003 · Cited by 1,005 · see citing works
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998 · see citing works
Self-citationTau positron emission tomographic imaging in aging and early <scp>A</scp> lzheimer disease
Johnson, K. A., Schultz, A., Betensky, R. A., Becker, J. A., Sepulcre, J., Rentz, D., Mormino, E., Chhatwal, J., Amariglio, R., Papp, K., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24546 · Cited by 986 · see citing works
Self-citationMurray, M. E., Graff-Radford, N. R., Ross, O. A., Petersen, R. C., Duara, R., & Dickson, D. W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70156-9 · Cited by 972 · see citing works
Alonso, A. D. C., Zaidi, T., Novák, M., Grundke, I., & Iqbal, K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121119298 · Cited by 968 · see citing works
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955 · see citing works
Aging, Memory, and Mild Cognitive Impairment
Petersen, R. C., Kokmen, E., Waring, S. C., Smith, G. E., Ivnik, R. J., & Tangelos, E. G. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297004717 · Cited by 895 · see citing works
Stamer, K., Vogel, R., Thies, E., Mandelkow, E., & Mandelkow, E.-M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200108057 · Cited by 885 · see citing works
Soto, C. A., Sigurdsson, E. M., Morelli, L., Kumar, R., Castaño, E. M., & Frangione, B. (1998) · Nature Medicine · doi:10.1038/nm0798-822 · Cited by 877 · see citing works
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870 · see citing works
Neuropathology of Alzheimer's Disease
Perl, D. P. (2010) · Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20157 · Cited by 825 · see citing works
Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics
de la Torre, J. C. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00683-0 · Cited by 834 · see citing works
López, J. A., González, H. M., & Léger, G. C. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00013-3 · Cited by 834 · see citing works
Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788 · see citing works
Petersen, R. C. (1995) · JAMA · doi:10.1001/jama.1995.03520400044042 · Cited by 783 · see citing works
Prion-like transmission of protein aggregates in neurodegenerative diseases
Brundin, P., Melki, R., & Kopito, R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2873 · Cited by 778 · see citing works
Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease
Bejanin, A., Schonhaut, D. R., La Joie, R., Kramer, J. H., Baker, S. L., Sosa, N., Ayakta, N., Cantwell, A., Janabi, M., Lauriola, M., et al. (2017) · Brain · doi:10.1093/brain/awx243 · Cited by 778 · see citing works
O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease
Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G. W., & Gong, C.-X. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400348101 · Cited by 775 · see citing works
Liu, F., Grundke‐Iqbal, I., Iqbal, K., & Gong, C. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04391.x · Cited by 759 · see citing works
Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00088 · Cited by 755 · see citing works
“…is a strong link between neocortical NFTs and cognitive decline (Tomlinson et al., 1970; Duyckaerts et al., 1990, 1997, 1998; Mckee et al., 1991; Arriagada et al., 1992; Bierer et al., 1995; Davis et al., 1995; Dickson et al., 1995; Nagy et al., 1995, 1999; Cummings et al., 1996; Berg et al.,…”
BackgroundThe Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials
Sperling, R., Mormino, E., & Johnson, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.038 · Cited by 725 · see citing works
Review: Alzheimer's Amyloid β-Peptide-Associated Free Radical Oxidative Stress and Neurotoxicity
Varadarajan, S., Yatin, S., Aksenova, M., & Butterfield, D. A. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4274 · Cited by 735 · see citing works
Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease
Masliah, E., Mallory, M., Alford, M., DeTeresa, R., Hansen, L. A., McKeel, D. W., & Morris, J. C. (2001) · Neurology · doi:10.1212/wnl.56.1.127 · Cited by 720 · see citing works
The Relationship between Aβ and Memory in the Tg2576 Mouse Model of Alzheimer's Disease
Westerman, M. A., Cooper-Blacketer, D., Mariash, A., Kotilinek, L., Kawarabayashi, T., Younkin, L. H., Carlson, G. A., Younkin, S. G., & Ashe, K. H. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01858.2002 · Cited by 714 · see citing works
Tau protein and the neurofibrillary pathology of Alzheimer's disease
Goedert, M. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90078-z · Cited by 718 · see citing works
Šimić, G., Leko, M. B., Wray, S., Harrington, C. R., Delalle, I., Milošević, N. J., Bažadona, D., Buée, L., de Silva, R., Giovanni, G. D., et al. (2016) · Biomolecules · doi:10.3390/biom6010006 · Cited by 698 · see citing works
Clinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702 · see citing works
Apolipoprotein E and Alzheimer disease.
Strittmatter, W. J., & Roses, A. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4725 · Cited by 699 · see citing works
Three dimensions of the amyloid hypothesis: time, space and 'wingmen'
Musiek, E. S., & Holtzman, D. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4018 · Cited by 697 · see citing works
Alzheimer' Disease as a Disconnection Syndrome?
Delbeuck, X., der Linden, M. V., & Collette, F. (2003) · Neuropsychology Review · doi:10.1023/a:1023832305702 · Cited by 708 · see citing works
Tau protein pathology in neurodegenerative diseases
Spillantini, M. G., & Goedert, M. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01337-x · Cited by 683 · see citing works
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F18]-T808
Chien, D. T., Szardenings, A. K., Bahri, S., Walsh, J. C., Mu, F., Xia, C. A., Shankle, W. R., Lerner, A. J., Su, M., Elizarov, A. M., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130098 · Cited by 676 · see citing works
Neuropathology of Cognitively Normal Elderly
Knopman, D. S., Parisi, J. E., Salviati, A., Floriach-Robert, M., Boeve, B. F., Ivnik, R. J., Smith, G. E., Dickson, D. W., Johnson, K. A., Petersen, L. E., et al. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.11.1087 · Cited by 674 · see citing works
Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain
Ingelsson, M., Fukumoto, H., Newell, K. L., Growdon, J. H., Hedley–Whyte, E. T., Frosch, M. P., Albert, M. S., Hyman, B. T., & Irizarry, M. C. (2004) · Neurology · doi:10.1212/01.wnl.0000115115.98960.37 · Cited by 666 · see citing works
Self-citationBerg, L., McKeel, D. W., Miller, J. P., Storandt, M., Rubin, E. H., Morris, J. C., Baty, J., Coats, M., Norton, J., Goate, A. M., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.326 · Cited by 657 · see citing works
the Dominantly Inherited Alzheimer Network, Barthélemy, N. R., Li, Y., Joseph-Mathurin, N., Gordon, B. A., Hassenstab, J., Benzinger, T. L. S., Buckles, V., Fagan, A. M., Perrin, R. J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0781-z · Cited by 651 · see citing works
Gong, C., & Iqbal, K. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708785909111 · Cited by 649 · see citing works
Hippocampus and entorhinal cortex in mild cognitive impairment and early AD
Pennanen, C., Kivipelto, M., Tuomainen, S., Hartikainen, P. H., Hänninen, T., Laakso, M. P., Hallikainen, M., Vanhanen, M., Nissinen, A. M., Helkala, E., et al. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00084-8 · Cited by 646 · see citing works
Lovell, M. A., Ehmann, W. D., Butler, S. M., & Markesbery, W. R. (1995) · Neurology · doi:10.1212/wnl.45.8.1594 · Cited by 644 · see citing works
Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181919a48 · Cited by 643 · see citing works
Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases
Guo, J. L., & Lee, V. M. Y. (2014) · Nature Medicine · doi:10.1038/nm.3457 · Cited by 641 · 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
Mechanisms of tau-induced neurodegeneration
Iqbal, K., Liu, F., Gong, C.-X., Alonso, A. D. C., & Grundke-Iqbal, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0486-3 · Cited by 628 · see citing works
Regionally specific loss of neurons in the aging human hippocampus.
West, M. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90113-p · Cited by 638 · 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
Xia, C., Arteaga, J., Chen, G., Gangadharmath, U., Gomez, L. F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V. P., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.11.008 · Cited by 605 · see citing works
Morris, J. C., Storandt, M., McKeel, D. W., Rubin, E. H., Price, J. L., Grant, E. A., & Berg, L. (1996) · Neurology · doi:10.1212/wnl.46.3.707 · Cited by 603 · see citing works
β-Amyloid fibrils induce tau phosphorylation and loss of microtubule binding
Busciglio, J., Lorenzo, A., Yeh, J., & Yankner, B. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90232-5 · Cited by 595 · see citing works
Tau protein aggregation is associated with cellular senescence in the brain
Musi, N., Valentine, J. M., Sickora, K. R., Baeuerle, E., Thompson, C. S., Shen, Q., & Orr, M. E. (2018) · Aging Cell · doi:10.1111/acel.12840 · Cited by 595 · see citing works
Functional Alterations in Memory Networks in Early Alzheimer’s Disease
Sperling, R. A., Dickerson, B. C., Pihlajamaki, M. M., Vannini, P., LaViolette, P. S., Vitolo, O. V., Hedden, T., Becker, J. A., Rentz, D. M., Selkoe, D. J., et al. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8109-7 · Cited by 587 · see citing works
Neurofibrillary Tangles, Amyloid, and Memory in Aging and Mild Cognitive Impairment
Guillozet-Bongaarts, A. L., Weıntraub, S., Mash, D. C., & Mesulam, M. M. (2003) · Archives of Neurology · doi:10.1001/archneur.60.5.729 · Cited by 572 · see citing works
Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease
Mehta, P. D., Pirttilä, T., Mehta, S. P., Sersen, E. A., Aisen, P. S., & Wisniewski, H. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.1.100 · Cited by 582 · see citing works
Neuronal activity regulates extracellular tau in vivo
Yamada, K., Holth, J. K., Liao, F., Stewart, F. R., Mahan, T. E., Jiang, H., Cirrito, J. R., Patel, T. K., Hochgräfe, K., Mandelkow, E., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131685 · Cited by 574 · see citing works
Matsuo, E. S., Shin, R., Billingsley, M., de Voorde, A. V., O'Connor, M., Trojanowski, J., & Lee, V. (1994) · Neuron · doi:10.1016/0896-6273(94)90264-x · Cited by 588 · see citing works
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
Do defecs in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?
Beal, M. F., Hyman, B. T., & Koroshetz, W. J. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90117-5 · Cited by 574 · see citing works
Self-citationWang, C., & Holtzman, D. M. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0478-5 · Cited by 589 · see citing works
Li, Y., Liu, L., Barger, S. W., & Griffin, W. S. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01605.2003 · Cited by 563 · see citing works
MRI measures of entorhinal cortex vs hippocampus in preclinical AD
Killiany, R., Hyman, B. T., Gómez‐Isla, T., Moss, M. B., Kikinis, R., Jolesz, F. A., Tanzi, R. E., Jones, K., & Albert, M. (2002) · Neurology · doi:10.1212/wnl.58.8.1188 · Cited by 564 · see citing works
Self-citationWang, J., Dickson, D. W., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7085 · Cited by 567 · see citing works
Proline-directed and non-proline-directed phosphorylation of PHF-tau
Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Yoshida, H., Titani, K., & Ihara, Y. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.823 · Cited by 557 · see citing works
Education modifies the relation of AD pathology to level of cognitive function in older persons
Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Mendes de Leon, C. F., Arnold, S. E., Barnes, L. L., & Bienias, J. L. (2003) · Neurology · doi:10.1212/01.wnl.0000069923.64550.9f · Cited by 549 · see citing works
Brain cytochrome oxidase in Alzheimer's disease
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537 · see citing works
Identification of oligomers at early stages of tau aggregation in Alzheimer's disease
Lasagna‐Reeves, C. A., Castillo‐Carranza, D. L., Sengupta, U., Sarmiento, J., Troncoso, J., Jackson, G. R., & Kayed, R. (2012) · The FASEB Journal · doi:10.1096/fj.11-199851 · Cited by 527 · see citing works
Insulin and Insulin-like Growth Factor-1 Regulate Tau Phosphorylation in Cultured Human Neurons*
Hong, M., & Lee, V. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19547 · Cited by 533 · see citing works
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
“Correlations between NFT density and clinical symptoms, such as a cognitive decline in AD, have been demonstrated [11, 12].”
Background
- Authors
- Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- ORCID
- Hyman, Bradley T.
- Venue
- Neurology
- Published
- 1992-03
- Volume
- 42
- Issue
- 3
- Pages
- 631-631
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2053116497
- Cited by
- 2,668
- References
- 0
- Citations by year
- 2026: 54 · 2025: 89 · 2024: 81 · 2023: 101 · 2022: 89 · 2021: 141 · 2020: 135 · 2019: 131 · 2018: 96 · 2017: 112 · 2016: 132 · 2015: 101 · 2014: 106 · 2013: 93 · 2012: 97
- FWCI
- 28.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-08487, P50 AG05134, P50AG005134)
- 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, amyloid plaques, dementia severity, disease duration, neuropathology, entorhinal cortex, hippocampal formation, amygdala, regional vulnerability, cytoarchitecture
- MeSH terms
- Aged, Alzheimer Disease, Amygdala, Brain, Female, Hippocampus, Humans, Male, Middle Aged, Neurofibrillary Tangles
About these checks
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