Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease
Abstract
Microtubule associated protein tau is abnormally phosphorylated in Alzheimer's disease (AD) and aggregates as paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). We show here that the pattern of tau phosphorylation correlates with the loss of neuronal integrity. Studies using 11 phosphorylation dependent tau antibodies and a panel of AD cases of varying severity were evaluated in terms of three stages of neurofibrillary tangle development: (1) pre-neurofibrillary tangle, (2) intra-, and (3) extra-neuronal neurofibrillary tangles. The pretangle state, in which neurons display nonfibrillar, punctate regions in the cytoplasm, sound dendrites, somas, and nuclei, was observed especially with phospho-tau antibodies TG3 (pT231), pS262, and pT153. Intraneuronal neurofibrillary tangles are homogenously stained with fibrillar tau structures, which were most prominently stained with pT175/181, 12E8 (pS262/pS356), pS422, pS46, pS214 antibodies. Extracellular NFTs, which contain substantial filamentous tau, are most prominently stained with AT8 (pS199/pS202/pT205), AT100 (pT212/pS214), and PHF-1 (pS396/pS404) antibodies, which also stain intracellular NFT. The sequence of early tau phosphorylation suggests that there are events prior to filament formation that are specific to particular phosphorylated tau epitopes, leading to conformational changes and cytopathological alterations.
Integrity signals
Registry
Cites
Statistics
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?
Specific tau phosphorylation epitopes are associated with different stages of neurofibrillary tangle formation in Alzheimer disease.
“Several groups have used phosphorylation-dependent tau antibodies and a panel of AD cases of varying severity to map epitopes that were associated with different stages of neurofibrillary tangle formation during disease progression (9, 10).”
From An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease (2013) · cites this paper as [9]
Thr(P)-231 is an epitope associated with early AD.
“an epitope that is associated with early AD (9)”
From An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease (2013) · cites this paper as [9]
Previous neuropathological findings highlighted that a key component of pre-tangle pathology was phosphorylation at threonine 231 and that CSF p-tau231 is an important discriminant of Braak 0-I from more advanced Braak stages.
“Previous neuropathological findings, which motivated the CSF assay development of p-tau231, highlighted that a key component of pre-tangle pathology was phosphorylation at threonine 23155 and that CSF p-tau231 is an important discriminant of Braak 0-I from more advanced Braak stages.56”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [55]
Tau phosphorylation at Ser262/356 is detected in the pre-tangle stage of neurons in AD brains.
“Tau phosphorylation at Ser262/356 is detected in the pre-tangle stage of neurons in AD brains [78].”
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
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 · see citing works
Self-citationMonoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205
Goedert, M., Jakes, R., & Vanmechelen, E. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11484-e · Cited by 608 · see citing works
Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488 · see citing works
Goedert, M., Jakes, R., Crowther, R. A., Cohen, P., Vanmechelen, E., Vandermeeren, M., & Cras, P. (1994) · Biochemical Journal · doi:10.1042/bj3010871 · Cited by 375 · see citing works
Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells
Sperbera, B. R., Leight, S., Goedert, M., & Lee, V. M.-Y. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11902-9 · Cited by 204 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Self-citationKetamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015198 · Cited by 1,260 · see citing works
Tau protein liquid–liquid phase separation can initiate tau aggregation
Wegmann, S., Eftekharzadeh, B., Tepper, K., Zoltowska, K. M., Bennett, R. E., Dujardin, S., Laskowski, P. R., MacKenzie, D., Kamath, T., Commins, C., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201798049 · Cited by 1,102 · see citing works
Self-citationTau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · see citing works
Tau protein kinases: Involvement in Alzheimer's disease
Martin, L., Latypova, X., Wilson, C. M., Magnaudeix, A., Perrin, M.-L., Yardin, C., & Terro, F. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.06.003 · Cited by 631 · see citing works
Tau phosphorylation in neuronal cell function and dysfunction
Johnson, G. V. W., & Stoothoff, W. H. (2004) · Journal of Cell Science · doi:10.1242/jcs.01558 · Cited by 624 · see citing works
Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710311114 · Cited by 517 · see citing works
“The tau monoclonal antibody, AT8, recognizes a double phosphorylation epitope (pS202, pT205) and has been shown to primarily stain intraneuronal and extraneuronal neurofibrillary tangles associated with Braak stages IV, V, and VI (24).”
BackgroundCaspase activation precedes and leads to tangles
de Calignon, A., Fox, L. M., Pitstick, R., Carlson, G. A., Bacskai, B. J., Spires-Jones, T. L., & Hyman, B. T. (2010) · Nature · doi:10.1038/nature08890 · Cited by 517 · see citing works
Self-citationAlzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012) · Scientific Reports · doi:10.1038/srep00700 · Cited by 502 · see citing works
SARS‐CoV‐2 targets neurons of 3D human brain organoids
Ramani, A., Müller, L., Ostermann, P. N., Gabriel, E., Abida‐Islam, P., Müller‐Schiffmann, A., Mariappan, A., Goureau, O., Gruell, H., Walker, A., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020106230 · Cited by 518 · see citing works
Jackson, G. R., Wiedau-Pazos, M., Sang, T.-K., Wagle, N., Brown, C. A., Massachi, S., & Geschwind, D. H. (2002) · Neuron · doi:10.1016/s0896-6273(02)00706-7 · Cited by 488 · see citing works
Hampel, H., Buerger, K., Zinkowski, R., Teipel, S. J., Goernitz, A., Andreasen, N., Sjoegren, M., DeBernardis, J., Kerkman, D., Ishiguro, K., et al. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.1.95 · Cited by 434 · see citing works
Suárez‐Calvet, M., Karikari, T. K., Ashton, N. J., Lantero Rodríguez, J., Milà‐Alomà, M., Gispert, J. D., Salvadó, G., Minguillon, C., Fauria, K., Shekari, M., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012921 · Cited by 401 · see citing works
Tau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · see citing works
Prabakaran, S., Lippens, G., Steen, H., & Gunawardena, J. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1185 · Cited by 335 · see citing works
Toward a unified scheme for the aggregation of tau into Alzheimer paired helical filaments
Barghorn, S., & Mandelkow, E. (2002) · Biochemistry · doi:10.1021/bi026469j · Cited by 341 · see citing works
Self-citationChronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration
Vyas, S., Rodrigues, A. J., Silva, J. M., Tronche, F., Almeida, O. F. X., Sousa, N., & Sotiropoulos, I. (2016) · Neural Plasticity · doi:10.1155/2016/6391686 · Cited by 297 · see citing works
Zempel, H., Luedtke, J., Kumar, Y., Biernat, J., Dawson, H., Mandelkow, E., & Mandelkow, E. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.207 · Cited by 283 · see citing works
Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278 · see citing works
Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies
Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., Xie, S. X., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Brain · doi:10.1093/brain/aws013 · Cited by 281 · see citing works
Rorabaugh, J. M., Chalermpalanupap, T., Botz-Zapp, C. A., Fu, V. M., Lembeck, N. A., Cohen, R. M., & Weinshenker, D. (2017) · Brain · doi:10.1093/brain/awx232 · Cited by 227 · see citing works
Ochalek, A., Mihalik, B., Avci, H. X., Chandrasekaran, A., Téglási, A., Bock, I., Giudice, M. L., Táncos, Z., Molnár, K., László, L., et al. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0317-z · Cited by 225 · see citing works
Zommer, N., Sergeant, N., Schraen-Maschke, S., Blum, D., & Buee, L. (2012) · Current Alzheimer Research · doi:10.2174/156720512800492503 · Cited by 193 · see citing works
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 · see citing works
Tau Phosphorylation Sites Work in Concert to Promote Neurotoxicity In Vivo
Steinhilb, M. L., Dias-Santagata, D., Fulga, T. A., Felch, D. L., & Feany, M. B. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-04-0327 · Cited by 187 · see citing works
Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease
Ashton, N. J., Benedet, A. L., Pascoal, T. A., Karikari, T. K., Lantero-Rodriguez, J., Brum, W. S., Mathotaarachchi, S., Therriault, J., Savard, M., Chamoun, M., et al. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.103836 · Cited by 184 · see citing works
ADF/Cofilin-Actin Rods in Neurodegenerative Diseases
Bamburg, J. R., Bernstein, B. W., Davis, R. C., Flynn, K. C., Goldsbury, C., Jensen, J. R., Maloney, M. T., Marsden, I. T., Minamide, L. S., Pak, C. W., et al. (2010) · Current Alzheimer Research · doi:10.2174/156720510791050902 · Cited by 173 · see citing works
Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β
Vossel, K. A., Xu, J. C., Fomenko, V., Miyamoto, T., Suberbielle, E., Knox, J. A., Ho, K., Kim, D. H., Yu, G.-Q., & Mucke, L. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201407065 · Cited by 167 · see citing works
Serrano-Pozo, A., William, C. M., Ferrer, I., Uro-Coste, E., Delisle, M.-B., Maurage, C.-A., Hock, C., Nitsch, R. M., Masliah, E., Growdon, J. H., et al. (2010) · Brain · doi:10.1093/brain/awq056 · Cited by 159 · see citing works
Self-citationGourmaud, S., Shou, H., Irwin, D. J., Sansalone, K., Jacobs, L. M., Lucas, T. H., Marsh, E. D., Davis, K. A., Jensen, F. E., & Talos, D. M. (2020) · Brain · doi:10.1093/brain/awz381 · Cited by 155 · see citing works
Barthélemy, N. R., Mallipeddi, N., Moiseyev, P., Sato, C., & Bateman, R. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00121 · Cited by 152 · see citing works
Tau accelerates α-synuclein aggregation and spreading in Parkinson’s disease
Pan, L., Li, C., Meng, L., Tian, Y., He, M., Yuan, X., Zhang, G., Zhang, Z., Xiong, J., Chen, G., et al. (2022) · Brain · doi:10.1093/brain/awac171 · Cited by 154 · see citing works
Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans
Kraemer, B. C., Burgess, J. K., Chen, J. H., Thomas, J. H., & Schellenberg, G. D. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl067 · Cited by 150 · see citing works
JNK Plays a Key Role in Tau Hyperphosphorylation in Alzheimer's Disease Models
Ploia, C., Antoniou, X., Sclip, A., Grande, V., Cardinetti, D., Colombo, A., Canu, N., Benussi, L., Ghidoni, R., Forloni, G., et al. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110320 · Cited by 145 · see citing works
An acetylation–phosphorylation switch that regulates tau aggregation propensity and function
Carlomagno, Y., Chung, D.-E. C., Yue, M., Castanedes-Casey, M., Madden, B. J., Dunmore, J., Tong, J., DeTure, M., Dickson, D. W., Petrucelli, L., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.794602 · Cited by 143 · see citing works
X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women
Yan, Y., Wang, X., Chaput, D., Shin, M.-K., Koh, Y., Gan, L., Pieper, A. A., Woo, J.-A. A., & Kang, D. E. (2022) · Cell · doi:10.1016/j.cell.2022.09.002 · Cited by 144 · see citing works
Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity
Wegmann, S., Maury, E. A., Kirk, M. J., Saqran, L., Roe, A., DeVos, S. L., Nicholls, S., Fan, Z., Takeda, S., Cagsal‐Getkin, O., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201592748 · Cited by 132 · see citing works
Self-citationCavallini, A., Brewerton, S., Bell, A., Sargent, S., Glover, S., Hardy, C., Moore, R., Calley, J., Ramachandran, D., Poidinger, M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.463984 · Cited by 133 · see citing works
“In addition, 4 of the 5 MAPK phosphorylated tau at pT231, an epitope that is associated with early AD (9).”
BackgroundMetformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy
Barini, E., Antico, O., Zhao, Y., Asta, F., Tucci, V., Catelani, T., Marotta, R., Xu, H., & Gasparini, L. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0082-7 · Cited by 126 · see citing works
Thomas, 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 · see citing works
Bussire, T., Gold, G., Kvari, E., Giannakopoulos, P., Bouras, C., Perl, D. P., Morrison, J. H., & Hof, P. R. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00942-9 · Cited by 122 · see citing works
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114 · see citing works
Tau biology, tauopathy, traumatic brain injury, and diagnostic challenges
Castellani, R. J., & Perry, G. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-180721 · Cited by 110 · see citing works
Ando, K., Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., & Iijima, K. M. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005917 · Cited by 105 · see citing works
Ojala, J. O., Sutinen, E. M., Salminen, A., & Pirttilä, T. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.09.012 · Cited by 102 · see citing works
A critical review of chronic traumatic encephalopathy
Iverson, G. L., Gardner, A. J., McCrory, P., Zafonte, R., & Castellani, R. J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.008 · Cited by 103 · see citing works
Sotiropoulos, I., Catania, C., Riedemann, T., Fry, J. P., Breen, K. C., Michaelidis, T. M., & Almeida, O. F. X. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05613.x · Cited by 97 · see citing works
Sottejeau, Y., Bretteville, A., Cantrelle, F.-X., Malmanche, N., Demiaute, F., Mendes, T., Delay, C., Alves Dos Alves, H., Flaig, A., Davies, P., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0237-8 · Cited by 98 · see citing works
“Indeed, Thr231 hyperphosphorylation occurs in the very early stages of neurofibrillary degeneration [21].”
The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
Fox, L. M., William, C. M., Adamowicz, D. H., Pitstick, R., Carlson, G. A., Spires-Jones, T. L., & Hyman, B. T. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318220a658 · Cited by 88 · see citing works
Self-citationAzorsa, D. O., Robeson, R. H., Frost, D., hoovet, B. M., Brautigam, G. R., Dickey, C., Beaudry, C., Basu, G. D., Holz, D. R., Hernandez, J. A., et al. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-25 · Cited by 88 · see citing works
Wang, J.-W., Imai, Y., & Lu, B. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5094-06.2007 · Cited by 80 · see citing works
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 · see citing works
Self-citationDiagnostic value of serum versus plasma phospho-tau for Alzheimer’s disease
Kac, P. R., Gonzalez-Ortiz, F., Simrén, J., Dewit, N., Vanmechelen, E., Zetterberg, H., Blennow, K., Ashton, N. J., & Karikari, T. K. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01011-w · Cited by 73 · see citing works
Iijima-Ando, K., Zhao, L., Gatt, A., Shenton, C., & Iijima, K. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq068 · Cited by 72 · see citing works
Hui, Y., Wang, D., Li, W., Zhang, L., Jin, J., Ma, N., Zhou, L., Nakajima, O., Zhao, W., & Gao, X. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102061 · Cited by 71 · see citing works
Developments in Tau PET Imaging
Zimmer, E. R., Leuzy, A., Gauthier, S., & Rosa-Neto, P. (2014) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2014.15 · Cited by 60 · see citing works
Davis, G. A., Castellani, R. J., & McCrory, P. (2015) · Neurosurgery · doi:10.1227/neu.0000000000000722 · Cited by 47 · see citing works
Spiegel, J., Pirraglia, E., Osorio, R. S., Glodzik, L., Li, Y., Tsui, W., Saint Louis, L. A., Randall, C., Butler, T., Xu, J., et al. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150167 · Cited by 45 · see citing works
Chronic Effects of Mild Neurotrauma: Putting the Cart Before the Horse?
Castellani, R. J., Perry, G., & Iverson, G. L. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000193 · Cited by 40 · see citing works
Schlegel, K., Awwad, K., Heym, R. G., Holzinger, D., Doell, A., Barghorn, S., Jahn, T. R., Klein, C., Mordashova, Y., Schulz, M., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0831-2 · Cited by 30 · see citing works
The metamorphic nature of the Tau protein: dynamic flexibility comes at a cost
Sabbagh, J. J., & Dickey, C. A. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00003 · Cited by 31 · see citing works
“…the MAPT gene and post-translational modifications such as phosphorylation and acetylation (Goedert et al., 1988; Hutton et al., 1998; Spillantini et al., 1998; Von Bergen et al., 2001; Augustinack et al., 2002; Cohen et al., 2011;Mandelkow andMandelkow, 2012; Cook et al., 2014; Min et al., 2015).”
BackgroundZimmer, E. R., Leuzy, A., Bhat, V., Gauthier, S., & Rosa-Neto, P. (2014) · Translational Neurodegeneration · doi:10.1186/2047-9158-3-6 · Cited by 30 · see citing works
Bachstetter, A. D., Morganti, J. M., Bodnar, C. N., Webster, S. J., Higgins, E. K., Roberts, K. N., Snider, H., Meier, S. E., Nation, G. K., Goulding, D. S., et al. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113180 · Cited by 29 · see citing works
Vautheny, A., Duwat, C., Aurégan, G., Joséphine, C., Hérard, A.-S., Jan, C., Mitja, J., Gipchtein, P., Gaillard, M.-C., Buée, L., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105398 · Cited by 28 · see citing works
Zhang, Z., Zhao, R., Tang, Y., Wen, S., Wang, D., & Qi, J. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0405-6 · Cited by 11 · see citing works
Retracted
- Authors
- Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Max Planck Unit for Structural Molecular Biology (DE)
- Corresponding author
- Hyman, Bradley T.
- Venue
- Acta Neuropathologica
- Published
- 2001-10-26
- Volume
- 103
- Issue
- 1
- Pages
- 26-35
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W1980768099
- Cited by
- 998
- References
- 6
- Citations by year
- 2026: 27 · 2025: 61 · 2024: 61 · 2023: 50 · 2022: 50 · 2021: 56 · 2020: 60 · 2019: 43 · 2018: 55 · 2017: 42 · 2016: 57 · 2015: 55 · 2014: 52 · 2013: 46 · 2012: 30
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- 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
- tau phosphorylation, Alzheimer's disease, neurofibrillary tangles, paired helical filaments, disease severity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Monoclonal, Antibody Specificity, Epitopes, Brain, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, Phosphorylation, Neurofibrillary Tangles, tau Proteins
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
