CoChat
Sign Up
Cited by 161Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The role of extracellular Tau in the spreading of neurofibrillary pathology

Open access
Medina, Miguel, Avila, Jesús·2014·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2014.00113PMC PMC4005959
Open this paper in CoChat — free accountOpen PDF

Abstract

The microtubule-associated protein (MAP) tau plays a critical role in the pathogenesis of Alzheimer's disease (AD) and several related disorders collectively known as tauopathies. Development of tau pathology is associated with progressive neuronal loss and cognitive decline. In the brains of AD patients, tau pathology spreads following an anatomically defined pattern. Mounting evidence strongly suggests that accumulation of abnormal tau is mediated through spreading of seeds of the protein from cell to cell and point at the involvement of extracellular tau species as the main agent in the interneuronal propagation of neurofibrillary lesions and spreading of tau toxicity throughout different brain regions in these disorders. That would support the concept that pathology initiates in a very small part of the brain many years before becoming symptomatic, spreading progressively to the whole brain within 10-20 years. Understanding the precise molecular mechanism underlying tau propagation is crucial for the development of therapeutics for this devastating disorder. In this work, we will discuss recent research on the role of extracellular tau in the spreading of tau pathology, through synaptic and non-synaptic mechanisms.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fncel.2014.00113

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Passive transfer of anti-tau antibodies is an effective method, since tau can be secreted into the extracellular space and some antibodies can enter neurons.

    “The passive transfer of anti-tau antibodies has also been shown to be an effective method, since it was reported that tau can be secreted into the extracellular space,535 and some antibodies even can enter neurons.531”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [535]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 98 · Cited by 161

Research works printed but not linked: 75

  1. Andreadis A. (2012). Tau splicing and the intricacies of dementia. J. Cell. Physiol. 227, 1220– 1225 10.1002/jcp.22842 21604267 PMC3177961 · DOI
  2. Barton A. J. Harrison P. J. Najlerahim A. Heffernan J. McDonald B. Robinson J. R. (1990). Increased tau messenger RNA in Alzheimer’s disease hippocampus. Am. J. Pathol. 137, 497– 502 2119143 PMC1877517
  3. Belkadi A. LoPresti P. (2008). Truncated Tau with the Fyn-binding domain and without the microtubule-binding domain hinders the myelinating capacity of an oligodendrocyte cell line. J. Neurochem. 107, 351– 360 10.1111/j.1471-4159.2008.05600.x 18680553 · DOI
  4. Braak H. Thal D. R. Ghebremedhin E. Del Tredici K. (2011). Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J. Neuropathol. Exp. Neurol. 70, 960– 969 10.1097/nen.0b013e318232a379 22002422 · DOI · Paper page
  5. Brady R. M. Zinkowski R. P. Binder L. I. (1995). Presence of tau in isolated nuclei from human brain. Neurobiol. Aging 16, 479– 486 10.1016/0197-4580(95)00023-8 7566354 · DOI
  6. Brandt R. Leger J. Lee G. (1995). Interaction of tau with the neural plasma membrane mediated by tau’s amino-terminal projection domain. J. Cell Biol. 131, 1327– 1340 10.1083/jcb.131.5.1327 8522593 PMC2120645 · DOI
  7. Caceres A. Kosik K. S. (1990). Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons. Nature 343, 461– 463 10.1038/343461a0 2105469 · DOI
  8. Chai X. Dage J. L. Citron M. (2012). Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol. Dis. 48, 356– 366 10.1016/j.nbd.2012.05.021 22668776 · DOI
  9. Cissé M. Halabisky B. Harris J. Devidze N. Dubal D. B. Sun B. (2011). Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 469, 47– 52 10.1038/nature09635 21113149 PMC3030448 · DOI · Paper page
  10. Dan A. Takahashi M. Masuda-Suzukake M. Kametani F. Nonaka T. Kondo H. (2013). Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain. Acta Neuropathol. Commun. 1: 54 10.1186/2051-5960-1-54 24252707 PMC3893535 · DOI
  11. Dawson H. N. Cantillana V. Jansen M. Wang H. Vitek M. P. Wilcock D. M. (2010). Loss of tau elicits axonal degeneration in a mouse model of Alzheimer’s disease. Neuroscience 169, 516– 531 10.1016/j.neuroscience.2010.04.037 20434528 PMC2900546 · DOI
  12. Díaz-Hernández M. Gomez-Ramos A. Rubio A. Gomez-Villafuertes R. Naranjo J. R. Miras-Portugal M. T. (2010). Tissue-nonspecific alkaline phosphatase promotes the neurotoxicity effect of extracellular tau. J. Biol. Chem. 285, 32539– 32548 10.1074/jbc.m110.145003 20634292 PMC2952256 · DOI
  13. Dickson J. R. Kruse C. Montagna D. R. Finsen B. Wolfe M. S. (2013). Alternative polyadenylation and miR-34 family members regulate tau expression. J. Neurochem. 127, 739– 749 10.1111/jnc.12437 24032460 PMC3859707 · DOI
  14. DiTella M. Feiguin F. Morfini G. Caceres A. (1994). Microfilament associated growth cone component depends upon Tau for its intracellular localization. Cell Motil. Cytoskeleton 29, 117– 130 10.1002/cm.970290204 7820862 · DOI
  15. Ferrer I. Santpere G. van Leeuwen F. W. (2008). Argyrophilic grain disease. Brain 131, 1416– 1432 10.1093/brain/awm305 18234698 · DOI
  16. Goedert M. Spillantini M. G. (2011). Pathogenesis of the tauopathies. J. Mol. Neurosci. 45, 425– 431 10.1007/s12031-011-9593-4 21785996 · DOI
  17. Goedert M. Spillantini M. G. Potier M. C. Ulrich J. Crowther R. A. (1989). Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J. 8, 393– 399 2498079 PMC400819
  18. Golde T. E. Lewis J. McFarland N. R. (2013). Anti-tauantibodies: hitting the target. Neuron 80, 254– 256 10.1016/j.neuron.2013.10.009 24139027 · DOI
  19. Gómez-Ramos A. Díaz-Hernández M. Cuadros R. Hernandez F. Avila J. (2006). Extracellular tau is toxic to neuronal cells. FEBS Lett. 580, 4842– 4850 10.1016/j.febslet.2006.07.078 16914144 · DOI · Paper page
  20. Gómez-Ramos A. Díaz-Hernández M. Rubio A. Díaz-Hernández J. I. Miras-Portugal M. T. Avila J. (2009). Characteristics and consequences of muscarinic receptor activation by tau protein. Eur. Neuropsychopharmacol. 19, 708– 717 10.1016/j.euroneuro.2009.04.006 19423301 · DOI
  21. Gómez-Ramos A. Díaz-Hernández M. Rubio A. Miras-Portugal M. T. Avila J. (2008). Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells. Mol. Cell. Neurosci. 37, 673– 681 10.1016/j.mcn.2007.12.010 18272392 · DOI
  22. Götz J. Xia D. Leinenga G. Chew Y. L. Nicholas H. (2013). What renders TAU toxic. Front. Neurol. 4: 72 10.3389/fneur.2013.00072 23772223 PMC3677143 · DOI
  23. Gu J. Sigurdsson E. M. (2011). Immunotherapy for tauopathies. J. Mol. Neurosci. 45, 690– 695 10.1007/s12031-011-9576-5 21739165 PMC3265133 · DOI
  24. Hanger D. P. Anderton B. H. Noble W. (2009). Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol. Med. 15, 112– 119 10.1016/j.molmed.2009.01.003 19246243 · DOI · Paper page
  25. Hanger D. P. Wray S. (2010). Tau cleavage and tau aggregation in neurodegenerative disease. Biochem. Soc. Trans. 38, 1016– 10120 10.1042/bst0381016 20658996 · DOI
  26. Himmler A. Drechsel D. Kirschner M. W. Martin D. W. Jr. (1989). Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. Mol. Cell. Biol. 9, 1381– 1388 2498649 PMC362554
  27. Hoover B. R. Reed M. N. Su J. Penrod R. D. Kotilinek L. A. Grant M. K. (2010). Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68, 1067– 1081 10.1016/j.neuron.2010.11.030 21172610 PMC3026458 · DOI · Paper page
  28. Iba M. Guo J. L. McBride J. D. Zhang B. Trojanowski J. Q. Lee V. M. (2013). Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer’s-like tauopathy. J. Neurosci. 33, 1024– 1037 10.1523/JNEUROSCI.2642-12.2013 23325240 PMC3575082 · DOI · Paper page
  29. Iqbal K. Liu F. Gong C. X. Alonso Adel C. Grundke-Iqbal I. (2009). Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 118, 53– 69 10.1007/s00401-009-0486-3 19184068 PMC2872491 · DOI · Paper page
  30. Ittner L. M. Ke Y. D. Delerue F. Bi M. Gladbach A. van Eersel J. (2010). Dendritic function of tau mediates amyloid-β toxicity in Alzheimer’s disease mouse models. Cell 142, 387– 397 10.1016/j.cell.2010.06.036 20655099 · DOI · Paper page
  31. Karch C. M. Jeng A. T. Goate A. M. (2012). Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathies. J. Biol. Chem. 287, 42751– 42762 10.1074/jbc.m112.380642 23105105 PMC3522274 · DOI
  32. Kaufman A. M. Milnerwood A. J. Sepers M. D. Coquinco A. She K. Wang L. (2012). Opposing roles of synaptic and extrasynaptic NMDA receptor signaling in cocultured striatal and cortical neurons. J. Neurosci. 32, 3992– 4003 10.1523/jneurosci.4129-11.2012 22442066 PMC6621208 · DOI
  33. Khatoon S. Grundke-Iqbal I. Iqbal K. (1992). Brain levels of microtubule-associated protein tau are elevated in Alzheimer’s disease: a radioimmuno-slot-blot assay for nanograms of the protein. J. Neurochem. 59, 750– 753 10.1111/j.1471-4159.1992.tb09432.x 1629745 · DOI
  34. Kim W. Lee S. Jung C. Ahmed A. Lee G. Hall G. F. (2010). Interneuronal transfer of human tau between Lamprey central neurons in situ. J. Alzheimers Dis. 19, 647– 664 10.3233/JAD-2010-1273 20110609 · DOI
  35. Klein C. Kramer E. M. Cardine A. M. Schraven B. Brandt R. Trotter J. (2002). Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau. J. Neurosci. 22, 698– 707 11826099 PMC6758498
  36. Koleske A. J. (2013). Molecular mechanisms of dendrite stability. Nat. Rev. Neurosci. 14, 536– 550 10.1038/nrn3486 23839597 PMC3947514 · DOI
  37. Kopeikina K. J. Hyman B. T. Spires-Jones T. L. (2012). Soluble forms of tau are toxic in Alzheimer’s disease. Transl. Neurosci. 3, 223– 233 10.2478/s13380-012-0032-y 23029602 PMC3460520 · DOI · Paper page
  38. Kovacech B. Skrabana R. Novak M. (2010). Transition of tau protein from disordered to misordered in Alzheimer’s disease. Neurodegener. Dis. 7, 24– 27 10.1159/000283478 20160453 · DOI
  39. Lee G. Newman S. T. Gard D. L. Band H. Panchamoorthy G. (1998). Tau interacts with src-family non-receptor tyrosine kinases. J. Cell Sci. 111, 3167– 3177 9763511
  40. Lee G. Thangavel R. Sharma V. M. Litersky J. M. Bhaskar K. Fang S. M. (2004). Phosphorylation of tau by fyn: implications for Alzheimer’s disease. J. Neurosci. 24, 2304– 2312 10.1523/jneurosci.4162-03.2004 14999081 PMC6730442 · DOI
  41. Li S. F. Wu M. N. Wang X. H. Yuan L. Yang D. Qi J. S. (2011). Requirement of α7 nicotinic acetylcholine receptors for amyloid β protein-induced depression of hippocampal long-term potentiation in CA1 region of rats in vivo. Synapse 65, 1136– 1143 10.1002/syn.20951 21584864 · DOI
  42. Liu L. Drouet V. Wu J. W. Witter M. P. Small S. A. Clelland C. (2012). Trans-synaptic spread of tau pathology in vivo. PLoS One 7: e31302 10.1371/journal.pone.0031302 22312444 PMC3270029 · DOI
  43. Liu F. Li B. Tung E. J. Grundke-Iqbal I. Iqbal K. Gong C. X. (2007). Site-specific effects of tau phosphorylation on its microtubule assembly activity and self-aggregation. Eur. J. Neurosci. 26, 3429– 3436 10.1111/j.1460-9568.2007.05955.x 18052981 PMC2262108 · DOI · Paper page
  44. Loomis P. A. Howard T. H. Castleberry R. P. Binder L. I. (1990). Identification of nuclear tau isoforms in human neuroblastoma cells. Proc. Natl. Acad. Sci. U S A 87, 8422– 8426 10.1073/pnas.87.21.8422 1700432 PMC54968 · DOI
  45. Magnoni S. Esparza T. J. Conte V. Carbonara M. Carrabba G. Holtzman D. M. (2012). Tau elevations in the brain extracellular space correlate with reduced amyloid-beta levels and predict adverse clinical outcomes after severe traumatic brain injury. Brain 135, 1268– 1280 10.1093/brain/awr286 22116192 PMC3326246 · DOI
  46. Marklund N. Blennow K. Zetterberg H. Ronne-Engstrom E. Enblad P. Hillered L. (2009). Monitoring of brain interstitial total tau and beta amyloid proteins by microdialysis in patients with traumatic brain injury. J. Neurosurg. 110, 1227– 1237 10.3171/2008.9.JNS08584 19216653 · DOI
  47. Maruyama M. Shimada H. Suhara T. Shinotoh H. Ji B. Maeda J. (2013). Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79, 1094– 1108 10.1016/j.neuron.2013.07.037 24050400 PMC3809845 · DOI · Paper page
  48. Medina M. (2011). Recent developments in tau-based therapeutics for neurodegenerative diseases. Recent Pat. CNS Drug Discov. 6, 20– 30 10.2174/157488911794079091 21118095 · DOI
  49. Medina M. Avila J. (2014). New perspectives on the role of tau in Alzheimer’s disease. Implications for therapy. Biochem. Pharmacol. 88, 540– 547 10.1016/j.bcp.2014.01.013 24462919 · DOI
  50. Nedergaard M. (2013). Garbage truck of the brain. Science 340, 1529– 1530 10.1126/science.1240514 23812703 PMC3749839 · DOI
  51. Pittman A. M. Fung H. C. de Silva R. (2006). Untangling the tau gene association with neurodegenerative disorders. Hum. Mol. Genet. 15, R188– R195 10.1093/hmg/ddl190 16987883 · DOI
  52. Plouffe V. Mohamed N. V. Rivest-McGraw J. Bertrand J. Lauzon M. Leclerc N. (2012). Hyperphosphorylation and cleavage at D421 enhance tau secretion. PLoS One 7: e36873 10.1371/journal.pone.0036873 22615831 PMC3352936 · DOI
  53. Pooler A. M. Phillips E. C. Lau D. H. Noble W. Hanger D. P. (2013). Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep. 14, 389– 394 10.1038/embor.2013.15 23412472 PMC3615658 · DOI · Paper page
  54. Poorkaj P. Bird T. D. Wijsman E. Nemens E. Garruto R. M. Anderson L. (1998). Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815– 825 10.1002/ana.410430617 9629852 · DOI · Paper page
  55. Qian W. Jin N. Shi J. Yin X. Jin X. Wang S. (2013). Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) enhances tau expression. J. Alzheimers Dis. 37, 529– 538 10.3233/JAD-130824 23948904 · DOI
  56. Rábano A. Rodal I. Cuadros R. Calero M. Hernández F. Ávila J. (2014). Argyrophylic grain pathology as a natural model of tau propagation. J. Alzheimers Dis. [Epub ahead of print]. 10.4137/jen.s12202 24577470 · DOI
  57. Rapoport M. Dawson H. N. Binder L. I. Vitek M. P. Ferreira A. (2002). Tauis essential to beta -amyloid-induced neurotoxicity. Proc. Natl. Acad. Sci. U S A 99, 6364– 6369 10.1073/pnas.092136199 11959919 PMC122954 · DOI · Paper page
  58. Roberson E. D. Scearce-Levie K. Palop J. J. Yan F. Cheng I. H. Wu T. (2007). Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science 316, 750– 754 10.1126/science.1141736 17478722 · DOI · Paper page
  59. Rodríguez-Martín T. Cuchillo-Ibáñez I. Noble W. Nyenya F. Anderton B. H. Hanger D. P. (2013). Tau phosphorylation affects its axonal transport and degradation. Neurobiol. Aging 34, 2146– 2157 10.1016/j.neurobiolaging.2013.03.015 23601672 PMC3684773 · DOI
  60. Seeley W. W. Crawford R. K. Zhou J. Miller B. L. Greicius M. D. (2009). Neurodegenerative diseases target large-scale human brain networks. Neuron 62, 42– 52 10.1016/j.neuron.2009.03.024 19376066 PMC2691647 · DOI · Paper page
  61. Selkoe D. J. (2002). Alzheimer’s disease is a synaptic failure. Science 298, 789– 791 10.1126/science.1074069 12399581 · DOI · Paper page
  62. Shi Y. Kirwan P. Smith J. MacLean G. Orkin S. H. Livesey F. J. (2012). A human stem cell model of early Alzheimer’s disease pathology in Down syndrome. Sci. Transl. Med. 4: 124ra129 10.1126/scitranslmed.3003771 22344463 PMC4129935 · DOI · Paper page
  63. Simón D. García-García E. Gómez-Ramos A. Falcón-Pérez J. M. Díaz-Hernández M. Hernández F. (2012b). Tau overexpression results in its secretion via membrane vesicles. Neurodegener. Dis. 10, 73– 75 10.1159/000334915 22269430 · DOI
  64. Simón D. Garcia-Garcia E. Royo F. Falcon-Perez J. M. Avila J. (2012a). Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Lett. 586, 47– 54 10.1016/j.febslet.2011.11.022 22138183 · DOI
  65. Simón D. Hernández F. Avila J. (2013). The involvement of cholinergic neurons in the spreading of tau pathology. Front. Neurol. 4: 74 10.3389/fneur.2013.00074 23785352 PMC3683623 · DOI
  66. Spillantini M. G. Goedert M. (2013). Tau pathology and neurodegeneration. Lancet Neurol. 12, 609– 622 10.1016/S1474-4422(13)70090-5 23684085 · DOI · Paper page
  67. Spillantini M. G. Murrell J. R. Goedert M. Farlow M. R. Klug A. Ghetti B. (1998). Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl. Acad. Sci. U S A 95, 7737– 7741 10.1073/pnas.95.13.7737 9636220 PMC22742 · DOI · Paper page
  68. Tackenberg C. Grinschgl S. Trutzel A. Santuccione A. C. Frey M. C. Konietzko U. (2013). NMDA receptor subunit composition determines beta-amyloid-induced neurodegeneration and synaptic loss. Cell Death Dis. 4: e608 10.1038/cddis.2013.129 23618906 PMC3641351 · DOI · Paper page
  69. Talantova M. Sanz-Blasco S. Zhang X. Xia P. Akhtar M. W. Okamoto S. (2013). Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation and synaptic loss. Proc. Natl. Acad. Sci. U S A 110, E2518– E2527 10.1073/pnas.1306832110 23776240 PMC3704025 · DOI · Paper page
  70. Tatebayashi Y. Iqbal K. Grundke-Iqbal I. (1999). Dynamic regulation of expression and phosphorylation of tau by fibroblast growth factor-2 in neural progenitor cells from adult rat hippocampus. J. Neurosci. 19, 5245– 5254 10377336 PMC6782310
  71. Terwel D. Dewachter I. Van Leuven F. (2002). Axonal transport, tau protein and neurodegeneration in Alzheimer’s disease. Neuromolecular Med. 2, 151– 165 10.1385/nmm:2:2:151 12428809 · DOI · Paper page
  72. Wang Y. Loomis P. A. Zinkowski R. P. Binder L. I. (1993). A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau. J. Cell Biol. 121, 257– 267 10.1083/jcb.121.2.257 8468346 PMC2200092 · DOI
  73. Wu J. W. Herman M. Liu L. Simoes S. Acker C. M. Figueroa H. (2013). Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J. Biol. Chem. 288, 1856– 1870 10.1074/jbc.M112.394528 23188818 PMC3548495 · DOI · Paper page
  74. Yamada K. Cirrito J. R. Stewart F. R. Jiang H. Finn M. B. Holmes B. B. (2011). In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J. Neurosci. 31, 13110– 13117 10.1523/jneurosci.2569-11.2011 21917794 PMC4299126 · DOI · Paper page
  75. Yanamandra K. Kfoury N. Jiang H. Mahan T. E. Ma S. Maloney S. E. (2013). Anti-tauantibodies that blocktauaggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80, 402– 414 10.1016/j.neuron.2013.07.046 24075978 PMC3924573 · DOI · Paper page

Authors
Medina, M., & Avila, J.
Affiliations
Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
ORCID
Medina, Miguel
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2014-04-23
Volume
8
Pages
113-113
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2014.00113
PMC
PMC4005959
OpenAlex
W2167935334
Cited by
161
References
98
Citations by year
2026: 5 · 2025: 14 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 18 · 2020: 15 · 2019: 20 · 2018: 23 · 2017: 13 · 2016: 8 · 2015: 13 · 2014: 6
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (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
extracellular tau, tauopathy, Alzheimer's disease, neurofibrillary pathology, tau propagation, prion-like seeding, synaptic transmission, tau toxicity

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