The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
Open accessAbstract
OBJECTIVE: To examine the relationship between stereologic estimates of AD-related pathology and severity of cognitive deficits in brain aging. BACKGROUND: Previous studies reported substantial contributions of neurofibrillary tangles (NFT), amyloid deposits, and neuronal loss to the development of dementia. However, the prediction of cognitive status based on nonstereologic quantification of these measures has led to conflicting results. Such studies have measured densities, rather than absolute numbers, and most do not take into account the potential interaction between the above pathologic hallmarks in a global multivariate analysis. METHODS: Clinicopathologic study in 22 elderly cases. Cognitive status assessed prospectively using the Mini-Mental State Examination (MMSE); stereologic assessment of NFT, unaffected neurons, and total amyloid volume in the CA1 field of the hippocampus, entorhinal cortex, and area 9. Statistical analysis was performed using both univariate and multivariate linear regression models. RESULTS: High total NFT counts but not amyloid volume were strongly associated with a lower number of unaffected neurons in all areas studied. A high proportion of variability in MMSE scores was explained by NFT and neuronal counts in the CA1 field (83% and 85.4%), entorhinal cortex (87.8% and 83.7%), and area 9 (87% and 79%); amyloid volume in the entorhinal cortex, but not in the CA1 field and area 9, accounted for 58.5% of MMSE variability. Multivariate analyses showed that total NFT counts in the entorhinal cortex and area 9 as well as neuron numbers in the CA1 field were the best predictors of MMSE score. CONCLUSIONS: These new stereologic data indicate that neuronal pathology in hippocampal formation and frontal cortex closely reflects the progression of cognitive deficits in brain aging and AD. They also demonstrate that amyloid volume has no additional predictive value, in terms of clinicopathologic correlations, beyond its interaction with NFT.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Even though extracellular amyloid plaque deposits had long been considered the principal players in the development and progression of AD, this association has been challenged by a poor correlation with the disease status [11]”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [11]
In the citing paper
“In particular, loss of neurons in the CA1 region of the hippocampus [22,23] and in the entorhinal cortex seems to correlate with the severity of memory deficits [11].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [11]
In the citing paper
“Cognitive impairment correlates with the number of neurofibrillary tangles137, which selectively affect highly connected pyramidal cells in association cortex but not in primary sensory cortex6,138,139.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [137]
In the citing paper
“Occurrence of Tau deposits correlates with the loss of cognitive functions in AD, suggesting a connection between Tau and synaptic transmission20.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [20]
In the citing paper
“The progression of tau pathology has been correlated with memory dysfunction and cognitive impairments in AD (DeVos et al., 2018; Giannakopoulos et al., 2003).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Giannakopoulos et al., 2003
In the citing paper
“pathological tau aggregates, in the absence of amyloid plaques, can induce neurotoxicity, chronic brain inflammation, and subsequent cognitive impairment in many primary human tauopathies, including Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration. 4 , 5 , 6”
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 [4]
In the citing paper
“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 [4]
In the citing paper
“Unlike Aβ, the stage of tau pathology correlates well with progression of cognitive impairment”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Giannakopoulos et al., 2003
In the citing paper
“Although apoE interacts with amyloid, it should be noted that plaque load does not correlate well with cognitive impairments, highlighted most obviously by people with substantial plaque burdens and normal cognition [67].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [67]
In the citing paper
“correlation of Tau pathology with cognitive decline in AD (Arriagada et al., 1992; Bierer et al., 1995; Giannakopoulos et al., 2003; Gómez-Isla et al., 1997)”
From Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease (2020) · cites this paper as Giannakopoulos et al., 2003
In the citing paper
“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 Giannakopoulos et al., 2003
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
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
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
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
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-citationCorrelation 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
Differences 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
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
Cited by
Sorted by citations
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Neuropathological 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
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Classification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031
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
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899
Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders
Mahley, R. W. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1427-y · Cited by 837
Ambadipudi, S., Biernat, J., Riedel, D., Mandelkow, E., & Zweckstetter, M. (2017) · Nature Communications · doi:10.1038/s41467-017-00480-0 · Cited by 782
Pike, K. E., Savage, G., Villemagne, V. L., Ng, S., Moss, S. A., Maruff, P., Mathis, C. A., Klunk, W. E., Masters, C. L., & Rowe, C. C. (2007) · Brain · doi:10.1093/brain/awm238 · Cited by 789
Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752
Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease
Wesseling, H., Mair, W., Kumar, M., Schlaffner, C. N., Tang, S., Beerepoot, P., Fatou, B., Guise, A. J., Cheng, L., Takeda, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.029 · Cited by 688
“, 1998) and correlation of Tau pathology with cognitive decline in AD (Arriagada et al., 1992; Bierer et al., 1995; Giannakopoulos et al., 2003; Gómez-Isla et al., 1997) have led to several mechanistic studies whose outcomes have underscored the importance of Tau in AD and other dementias (Mudher et al.”
BackgroundTau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Brier, M. R., Gordon, B., Friedrichsen, K., McCarthy, J., Stern, A., Christensen, J., Owen, C., Aldea, P., Su, Y., Hassenstab, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2362 · Cited by 734
Alzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689
“This topography of the lesions corresponds to the evolution of the symptoms of AD [48].”
BackgroundEarly 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
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609
Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
Frisoni, G. B., Boccardi, M., Barkhof, F., Blennow, K., Cappa, S., Chiotis, K., Démonet, J.-F., Garibotto, V., Giannakopoulos, P., Gietl, A., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30159-x · Cited by 626
Self-citationAlzheimer's Disease: From Pathology to Therapeutic Approaches
Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626
Halagappa, V. K. M., Guo, Z., Pearson, M., Matsuoka, Y., Cutler, R. G., LaFerla, F. M., & Mattson, M. P. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.019 · Cited by 580
In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum
Cho, H., Choi, J. Y., Hwang, M. S., Kim, Y. J., Lee, H. M., Lee, H. S., Lee, J. H., Ryu, Y. H., Lee, M. S., & Lyoo, C. H. (2016) · Annals of Neurology · doi:10.1002/ana.24711 · Cited by 499
Bennett, D. A., Schneider, J. A., Wilson, R. S., Bienias, J. L., & Arnold, S. E. (2004) · Archives of Neurology · doi:10.1001/archneur.61.3.378 · Cited by 526
Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer’s Disease
Serrano-Pozo, A., Mielke, M. L., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Frosch, M. P., & Hyman, B. T. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.05.047 · Cited by 488
Morales, I., Guzmán-MartÃnez, L., Cerda-Troncoso, C., FarÃas, G. A., & Maccioni, R. B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00112 · Cited by 490
An autoradiographic evaluation of AV-1451 Tau PET in dementia
Lowe, V. J., Curran, G., Fang, P., Liesinger, A. M., Josephs, K. A., Parisi, J. E., Kantarci, K., Boeve, B. F., Pandey, M. K., Bruinsma, T., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0315-6 · Cited by 474
Model‐guided microarray implicates the retromer complex in Alzheimer's disease
Small, S. A., Kent, K., Pierce, A., Leung, C., Kang, M. S., Okada, H., Honig, L., Vonsattel, J., & Kim, T. (2005) · Annals of Neurology · doi:10.1002/ana.20667 · Cited by 440
Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438
McManus, M. J., Murphy, M. P., & Franklin, J. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0552-11.2011 · Cited by 432
A Systems Level Analysis of Transcriptional Changes in Alzheimer's Disease and Normal Aging
Miller, J. A., Oldham, M. C., & Geschwind, D. H. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4098-07.2008 · Cited by 385
Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases
Chi, H., Chang, H.-Y., & Sang, T.-K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103082 · Cited by 412
Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology
Perez-Nievas, B. G., Stein, T. D., Tai, H.-C., Dols-Icardo, O., Scotton, T. C., Barroeta-Espar, I., Fernandez-Carballo, L., de Munain, E. L., Perez, J., Marquie, M., et al. (2013) · Brain · doi:10.1093/brain/awt171 · Cited by 387
Anti-Aβ Therapeutics in Alzheimer's Disease: The Need for a Paradigm Shift
Golde, T. E., Schneider, L. S., & Koo, E. H. (2011) · Neuron · doi:10.1016/j.neuron.2011.01.002 · Cited by 382
Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease
Arnsten, A. F. T., Datta, D., Del Tredici, K., & Braak, H. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12192 · Cited by 361
Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy
Schaeffer, V., Lavenir, I., Ozcelik, S., Tolnay, M., Winkler, D. T., & Goedert, M. (2012) · Brain · doi:10.1093/brain/aws143 · Cited by 343
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336
Soluble protein oligomers as emerging toxins in Alzheimer’s and other amyloid diseases
Ferreira, S. T., Vieira, M. N. N., & De Felice, F. G. (2007) · IUBMB Life · doi:10.1080/15216540701283882 · Cited by 335
High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model
Julien, C., Tremblay, C., Phivilay, A., Berthiaume, L., Émond, V., Julien, P., & Calon, F. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.022 · Cited by 288
Emerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297
Nelson, P. T., Jicha, G. A., Schmitt, F. A., Liu, H., Davis, D. G., Mendiondo, M. S., Abner, E. L., & Markesbery, W. R. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e31815c5efb · Cited by 292
Changing perspectives regarding late-life dementia
Fotuhi, M., Hachinski, V., & Whitehouse, P. J. (2009) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.175 · Cited by 291
Tracy, T. E., Sohn, P. D., Minami, S. S., Wang, C., Min, S.-W., Li, Y., Zhou, Y., Le, D., Lo, I., Ponnusamy, R., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.005 · Cited by 277
TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
Martini-Stoica, H., Cole, A. L., Swartzlander, D. B., Chen, F., Wan, Y.-W., Bajaj, L., Bader, D. A., Lee, V. M. Y., Trojanowski, J. Q., Liu, Z., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20172158 · Cited by 253
Wischik, C. M., Staff, R. T., Wischik, D. J., Bentham, P., Murray, A. D., Storey, J. M. D., Kook, K. A., & Harrington, C. R. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142874 · Cited by 269
Kaufman, S. K., Del Tredici, K., Thomas, T. L., Braak, H., & Diamond, M. I. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1855-6 · Cited by 259
Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1449-5 · Cited by 235
Soluble forms of tau are toxic in Alzheimer's disease
Kopeikina, K., Hyman, B., & Spires-Jones, T. (2012) · Translational Neuroscience · doi:10.2478/s13380-012-0032-y · Cited by 232
Sontag, E., Luangpirom, A., Hladik, C., Mudrak, I., Ogris, E., Speciale, S., & White, C. L. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.4.287 · Cited by 228
Mechanisms of Protein Seeding in Neurodegenerative Diseases
Walker, L. C., Diamond, M. I., Duff, K. E., & Hyman, B. T. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.1453 · Cited by 226
Dendritic Spine Pathology in Neurodegenerative Diseases
Herms, J., & Dorostkar, M. M. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044216 · Cited by 201
Cortical Microinfarcts and Demyelination Significantly Affect Cognition in Brain Aging
Kövari, E., Gold, G., Herrmann, F. R., Canuto, A., Hof, P. R., Michel, J.-P., Bouras, C., & Giannakopoulos, P. (2004) · Stroke · doi:10.1161/01.str.0000110791.51378.4e · Cited by 202
Self-citationChen, J. J., Nathaniel, D. L., Raghavan, P., Nelson, M., Tian, R., Tse, E., Hong, J. Y., See, S. K., Mok, S.-A., Hein, M. Y., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009432 · Cited by 170
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183
Bussière, T., Giannakopoulos, P., Bouras, C., Perl, D. P., Morrison, J. H., & Hof, P. R. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10760 · Cited by 185
Self-citationGordon, B. A., Friedrichsen, K., Brier, M., Blazey, T., Su, Y., Christensen, J., Aldea, P., McConathy, J., Holtzman, D. M., Cairns, N. J., et al. (2016) · Brain · doi:10.1093/brain/aww139 · Cited by 184
Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis
Roussarie, J.-P., Yao, V., Rodriguez-Rodriguez, P., Oughtred, R., Rust, J., Plautz, Z., Kasturia, S., Albornoz, C., Wang, W., Schmidt, E. F., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.010 · Cited by 180
Self-citationAmyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?
Panza, F., Lozupone, M., Seripa, D., & Imbimbo, B. P. (2019) · Annals of Neurology · doi:10.1002/ana.25410 · Cited by 178
TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice
Jiang, T., Zhang, Y.-D., Chen, Q., Gao, Q., Zhu, X.-C., Zhou, J.-S., Shi, J.-Q., Lu, H., Tan, L., & Yu, J.-T. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.028 · Cited by 176
Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer’s disease
Zheng, Y., Liu, A., Wang, Z.-J., Cao, Q., Wang, W., Lin, L., Ma, K., Zhang, F., Wei, J., Matas, E., et al. (2019) · Brain · doi:10.1093/brain/awy354 · Cited by 168
Alzheimer disease pathology as a host response
Castellani, R. J., Lee, H.-G., Zhu, X., Perry, G., & Smith, M. A. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318177eaf4 · Cited by 171
Tau Oligomers: The Toxic Player at Synapses in Alzheimer’s Disease
Guerrero-Muñoz, M. J., Gerson, J., & Castillo-Carranza, D. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00464 · Cited by 168
. Identification of Alzheimer and vascular lesion thresholds for mixed dementia.
Gold, G., Giannakopoulos, P., Herrmann, F. R., Bouras, C., & Kovari, E. (2007) · Brain · doi:10.1093/brain/awm228 · Cited by 163
Self-citationAD-linked R47H- TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation
Sayed, F. A., Kodama, L., Fan, L., Carling, G. K., Udeochu, J. C., Le, D., Li, Q., Zhou, L., Wong, M. Y., Horowitz, R., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe3947 · Cited by 155
Cabrales Fontela, Y., Kadavath, H., Biernat, J., Riedel, D., Mandelkow, E., & Zweckstetter, M. (2017) · Nature Communications · doi:10.1038/s41467-017-02230-8 · Cited by 148
Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of Alzheimer’s disease
Branca, C., Ferreira, E., Nguyen, T.-V., Doyle, K., Caccamo, A., & Oddo, S. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx361 · Cited by 139
Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer’s Disease
Cristóvão, J. S., Santos, R., & Gomes, C. M. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/9812178 · Cited by 146
Mild cognitive impairment with suspected nonamyloid pathology (SNAP): Prediction of progression
Caroli, A., Prestia, A., Galluzzi, S., Ferrari, C., van der Flier, W. M., Ossenkoppele, R., Van Berckel, B., Barkhof, F., Teunissen, C., Wall, A. E., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001209 · Cited by 142
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas, C. D., Carlyle, B. C., Leslie, S., Preuss, T. M., Crimins, J. L., Huttner, A. J., van Dyck, C. H., Rosene, D. L., Nairn, A. C., & Arnsten, A. F. T. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.11.005 · Cited by 140
cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex
Carlyle, B. C., Nairn, A. C., Wang, M., Yang, Y., Jin, L. E., Simen, A. A., Ramos, B. P., Bordner, K. A., Craft, G. E., Davies, P., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322360111 · Cited by 139
Thal, D. R., Griffin, W. S. T., & Braak, H. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00411.x · Cited by 134
Down-regulation of WW Domain-containing Oxidoreductase Induces Tau Phosphorylation in Vitro
Sze, C.-I., Su, M., Pugazhenthi, S., Jambal, P., Hsu, L.-J., Heath, J., Schultz, L., & Chang, N.-S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401399200 · Cited by 130
Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia
Kövari, E., Gold, G., Herrmann, F. R., Canuto, A., Hof, P. R., Bouras, C., & Giannakopoulos, P. (2007) · Neurology · doi:10.1212/01.wnl.0000257094.10655.9a · Cited by 128
Self-citationThomas, S. N., Funk, K. E., Wan, Y., Liao, Z., Davies, P., Kuret, J., & Yang, A. J. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0893-0 · Cited by 123
Rudrabhatla, P., Jaffe, H., & Pant, H. C. (2011) · The FASEB Journal · doi:10.1096/fj.11-181297 · Cited by 121
Jiang, T., Tan, L., Zhu, X.-C., Zhou, J.-S., Cao, L., Tan, M.-S., Wang, H.-F., Chen, Q., Zhang, Y.-D., & Yu, J.-T. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.08.019 · Cited by 111
Gaikwad, S., Senapati, S., Haque, M. A., & Kayed, R. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13490 · Cited by 117
Rubenstein, R., Chang, B., Davies, P., Wagner, A. K., Robertson, C. S., & Wang, K. K. W. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3548 · Cited by 116
Bell, W. R., An, Y., Kageyama, Y., English, C., Rudow, G. L., Pletnikova, O., Thambisetty, M., O'Brien, R., Moghekar, A. R., Albert, M. S., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.07.215 · Cited by 111
CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology
Mittal, K., Eremenko, E., Berner, O., Elyahu, Y., Strominger, I., Apelblat, D., Nemirovsky, A., Spiegel, I., & Monsonego, A. (2019) · iScience · doi:10.1016/j.isci.2019.05.039 · Cited by 114
Chronic cerebral hypoperfusion accelerates amyloid β deposition in APPSwInd transgenic mice
Kitaguchi, H., Tomimoto, H., Ihara, M., Shibata, M., Uemura, K., Kalaria, R. N., Kihara, T., Asada-Utsugi, M., Kinoshita, A., & Takahashi, R. (2009) · Brain Research · doi:10.1016/j.brainres.2009.07.078 · Cited by 108
Li, H., Liu, C.-C., Zheng, H., & Huang, T. Y. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0139-3 · Cited by 103
Aerobic glycolysis in the primate brain: Reconsidering the implications for growth and maintenance
Bauernfeind, A. L., Barks, S. K., Duka, T., Grossman, L. I., Hof, P. R., & Sherwood, C. C. (2014) · Brain Structure and Function · doi:10.1007/s00429-013-0662-z · Cited by 105
Self-citationMorphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?
Imhof, A., Kövari, E., von Gunten, A., Gold, G., Rivara, C.-B., Herrmann, F. R., Hof, P. R., Bouras, C., & Giannakopoulos, P. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.025 · Cited by 106
Self-citationDistinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.906 · Cited by 104
Pathological Substrates of Cognitive Decline in Alzheimer’s Disease
Giannakopoulos, P., Kövari, E., Gold, G., von Gunten, A., Hof, P. R., & Bouras, C. (2009) · Frontiers of Neurology and Neuroscience · doi:10.1159/000197881 · Cited by 101
Self-citationCognitive impact of neuronal pathology in the entorhinal cortex and CA1 field in Alzheimer's disease
GUNTEN, A., KOVARI, E., BUSSIERE, T., RIVARA, C., GOLD, G., BOURAS, C., HOF, P., & GIANNAKOPOULOS, P. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.02.008 · Cited by 101
Plaque-associated local toxicity increases over the clinical course of Alzheimer disease
Serrano-Pozo, A., Betensky, R. A., Frosch, M. P., & Hyman, B. T. (2016) · The American Journal of Pathology · doi:10.1016/j.ajpath.2015.10.010 · Cited by 100
Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease
Vandenberghe, R., Adamczuk, K., Dupont, P., Laere, K. V., & Chételat, G. (2013) · NeuroImage: Clinical · doi:10.1016/j.nicl.2013.03.014 · Cited by 99
“…in the dentate gyrus and correlated to episodic memory scores (Scheff et al., 2006) • Neuronal loss, starting in entorhinal cortex (Gómez-Isla et al., 1996), and correlated to cognitive scores (Giannakopoulos et al., 2003) • Neurofibrillary tangles (NFT) andneuropil threads (Hymanet al., 2012).”
BackgroundInfluentialTargeting tau: clinical trials and novel therapeutic approaches
VandeVrede, L., Boxer, A. L., & Polydoro, M. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134919 · Cited by 90
Perez, S. E., Raghanti, M. A., Hof, P. R., Kramer, L., Ikonomovic, M. D., Lacor, P. N., Erwin, J. M., Sherwood, C. C., & Mufson, E. J. (2013) · Journal of Comparative Neurology · doi:10.1002/cne.23428 · Cited by 95
“Clinical pathological studies have demonstrated that, unlike diffuse plaques, neuritic plaques as well as the amount and distribution of NFT correlate with cognitive decline in AD (Arriagada et al., 1992; Nagy et al., 1995; Gomez-Isla et al., 1996; Giannakopoulos et al., 2003).”
BackgroundSelf-citationBACE inhibitors in clinical development for the treatment of Alzheimer’s disease
Panza, F., Lozupone, M., Solfrizzi, V., Sardone, R., Piccininni, C., Dibello, V., Stallone, R., Giannelli, G., Bellomo, A., Greco, A., et al. (2018) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2018.1531706 · Cited by 92
Wang, L., Bharti, Kumar, R., Pavlov, P. F., & Winblad, B. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112915 · Cited by 92
Wattmo, C., Blennow, K., & Hansson, O. (2020) · BMC Neurology · doi:10.1186/s12883-019-1591-0 · Cited by 93
Alzheimer's Disease: The Downside of a Highly Evolved Parietal Lobe?
Bruner, E., & Jacobs, H. I. L. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-122299 · Cited by 87
Dendritic Spines: Mediators of Cognitive Resilience in Aging and Alzheimer’s Disease
Walker, C. K., & Herskowitz, J. H. (2021) · The Neuroscientist · doi:10.1177/1073858420945964 · Cited by 86
Saul, A., Sprenger, F., Bayer, T. A., & Wirths, O. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.05.003 · Cited by 88
Arnsten, A. F. T., Datta, D., Leslie, S., Yang, S.-T., Wang, M., & Nairn, A. C. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903671116 · Cited by 74
Transcriptional and conformational changes of the tau molecule in Alzheimer's disease
Hyman, B. T., Augustinack, J. C., & Ingelsson, M. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.06.015 · Cited by 79
Sabbagh, M. N., Cooper, K., DeLange, J., Stoehr, J. D., Thind, K., Lahti, T., Reisberg, B., Sue, L., Vedders, L., Fleming, S. R., et al. (2010) · Current Alzheimer Research · doi:10.2174/156720510791162340 · Cited by 79
Lim, Y. Y., Hassenstab, J., Cruchaga, C., Goate, A., Fagan, A. M., Benzinger, T. L. S., Maruff, P., Snyder, P. J., Masters, C. L., Allegri, R., et al. (2016) · Brain · doi:10.1093/brain/aww200 · Cited by 76
Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models
Wirths, O., & Zampar, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218144 · Cited by 75
“Even though extracellular amyloid plaque deposits had long been considered the principal players in the development and progression of AD, this association has been challenged by a poor correlation with the disease status [11] and therefore other options, such as the potential toxic effects of intraneuronal Aβ accumul…”
BackgroundMisfolded Truncated Protein τ Induces Innate Immune Response via MAPK Pathway
Kovac, A., Zilka, N., Kazmerova, Z., Cente, M., Zilkova, M., & Novak, M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100216 · Cited by 75
Metadata
- Authors
- Giannakopoulos, P., Herrmann, F. R., Bussière, T., Bouras, C., Kövari, E., Perl, D. P., Morrison, J. H., Gold, G., & Hof, P. R.
- Affiliations
- University of Geneva (CH)
- From the Departments of Psychiatry (Drs. Giannakopoulos, Bouras, and Kövari) and Geriatrics (Drs. Herrmann and Gold), HUG Belle-Idée, University of Geneva School of Medicine; Department of Psychogeriatrics (Dr. Giannakopoulos), University of Lausanne School of Medicine, Switzerland; Kastor Neurobiology of Aging Laboratories and Fishberg Research Center for Neurobiology (Drs. Bussière, Bouras, Perl, Morrison, and Hof) and Departments of Geriatrics and Adult Development (Drs. Morrison and Hof),...
- Venue
- Neurology
- Published
- 2003-05-13
- Volume
- 60
- Issue
- 9
- Pages
- 1495-1500
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2066792703
- Cited by
- 1,118
- References
- 49
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 57 · 2023: 60 · 2022: 64 · 2021: 72 · 2020: 87 · 2019: 64 · 2018: 65 · 2017: 54 · 2016: 62 · 2015: 56 · 2014: 56 · 2013: 45 · 2012: 51
- FWCI
- 11.66
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Funders
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, P01AG002219)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, neurofibrillary tangles, amyloid plaques, neuronal loss, cognitive decline, stereology, hippocampal CA1, entorhinal cortex, frontal cortex, amygdala, Mini-Mental State Examination, dementia prediction, clinicopathological correlation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Female, Frontal Lobe, Hippocampus, Humans, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Severity of Illness Index, Single-Blind Method, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Entorhinal Cortex
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
