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Cited by 109Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchPrion Diseases and Protein Misfolding

Different tau species lead to heterogeneous tau pathology propagation and misfolding

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Dujardin, Simon, Bégard, Séverine, Caillierez, Raphaëlle, Lachaud, Cédrick, Carrier, Sébastien, Lieger, Sarah, Gonzalez, Jose A., Deramecourt, Vincent +6 more·2018·Acta Neuropathologica Communications
DOI 10.1186/s40478-018-0637-7PMC PMC6263555
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Abstract

Tauopathies are a heterogeneous group of pathologies characterized by tau aggregation inside neurons. Most of them are sporadic but certain tauopathies rely on tau gene (MAPT) mutations. They particularly differ from one to another by their different neuropathological signatures e.g. lesion shapes, regions affected and molecular composition of aggregates. Six isoforms of tau exist, but they do not all co-aggregate in each tauopathy but rather have a unique signature for each one. In some tauopathies such as Alzheimer's disease (AD), tau protein aggregation follows stereotypical anatomical stages. Recent data suggest that this progression is due to an active process of tau protein propagation from neuron-to-neuron. We wondered how tau isoforms or mutations could influence the process of tau aggregation and tau propagation. In human neuropathological material, we found that MAPT mutations induce a faster misfolding compared to tau found in sporadic AD patients. In the rat brain, we observed cell-to-cell transfer of non-pathological tau species irrespective of the tested isoform or presence of a mutation. By contrast, we found that the species of tau impact the propagation of tau pathology markers such as hyperphosphorylation and misfolding. Indeed, misfolding and hyperphosphorylated tau proteins do not spread at the same rate when tau is mutated, or the isoform composition is modified. These results clearly argue for the existence of specific folding properties of tau depending on isoforms or mutations impacting the behavior of pathological tau species.

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  • The specific folded tau could be energetically more favourable for accelerated transformation of ptau to NFT tau in the presence of additional proteinopathy such as Aβ.

    “This may be related to the fact that this specific type of folded tau could be energetically more favourable for accelerated transformation of ptau to NFT tau in the presence of additional proteinopathy such as Aβ (26, 27).”

    From Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation (2022) · cites this paper as [26]

    The Introduction and Discussion (no page available) describe tau hyperphosphorylation, misfolding and aggregation, and suggest that different tau species have different folding properties. They do not say that a particular fold is energetically more favourable or that Aβ accelerates the transformation of phosphorylated tau into neurofibrillary tangles. (LLM, conf=0.85)

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Research works printed but not linked: 59

  1. [1]Ahmed Z Cooper J Murray TK Garn K McNaughton E Clarke H Parhizkar S Ward MA Cavallini A Jackson S Bose sS Clavaguera F Tolnay M Lavenir I Goedert M Hutton ML O'Neill MJ A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity Acta Neuropathol 2014 127 667 683 10.1007/s00401-014-1254-6 24531916 PMC4252866 · DOI
  2. [2]Aoyagi H Hasegawa M Tamaoka A Fibrillogenic nuclei composed of P301L mutant tau induce elongation of P301L tau but not wild-type tau J Biol Chem 2007 282 20309 20318 10.1074/jbc.M611876200 17526496 · DOI
  3. [4]Barghorn S Zheng-Fischhofer Q Ackmann M Biernat J von Bergen M Mandelkow EM Mandelkow E Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias Biochemistry 2000 39 11714 11721 10.1021/bi000850r 10995239 · DOI
  4. [5]Biernat J Gustke N Drewes G Mandelkow EM Mandelkow E Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding Neuron 1993 11 153 163 10.1016/0896-6273(93)90279-Z 8393323 · DOI · Paper page
  5. [8]Buee L Bussiere T Buee-Scherrer V Delacourte A Hof PR Tau protein isoforms, phosphorylation and role in neurodegenerative disorders Brain Res Brain Res Rev 2000 33 95 130 10.1016/S0165-0173(00)00019-9 10967355 · DOI
  6. [9]Butner KA Kirschner MW Tau protein binds to microtubules through a flexible array of distributed weak sites J Cell Biol 1991 115 717 730 10.1083/jcb.115.3.717 1918161 PMC2289193 · DOI · Paper page
  7. [10]Caillierez R Begard S Lecolle K Deramecourt V Zommer N Dujardin S Loyens A Dufour N Auregan G Winderickx J Hantraye P Deglon N Buee L Colin M Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain Mol Ther 2013 21 1358 1368 10.1038/mt.2013.66 23609018 PMC3702115 · DOI
  8. [11]Chai X Dage JL Citron M Constitutive secretion of tau protein by an unconventional mechanism Neurobiol Dis 2012 48 356 366 10.1016/j.nbd.2012.05.021 22668776 · DOI
  9. [12]Chang E Kim S Yin H Nagaraja HN Kuret J Pathogenic missense MAPT mutations differentially modulate tau aggregation propensity at nucleation and extension steps J Neurochem 2008 107 1113 1123 10.1111/j.1471-4159.2008.05692.x 18803694 PMC2596975 · DOI
  10. [15]Delacourte A David JP Sergeant N Buee L Wattez A Vermersch P Ghozali F Fallet-Bianco C Pasquier F Lebert F Petit H Di Menza C The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease Neurology 1999 52 1158 1165 10.1212/WNL.52.6.1158 10214737 · DOI · Paper page
  11. [16]Deramecourt V Lebert F Maurage CA Fernandez-Gomez FJ Dujardin S Colin M Sergeant N Buee-Scherrer V Clot F Ber IL Brice A Pasquier F Buee L Clinical, neuropathological, and biochemical characterization of the novel tau mutation P332S J Alzheimers Dis 2012 31 741 749 10.3233/JAD-2012-120160 22699846 · DOI
  12. [17]Dujardin S Begard S Caillierez R Lachaud C Delattre L Carrier S Loyens A Galas MC Bousset L Melki R Auregan G Hantraye P Brouillet E Buee L Colin M Ectosomes: a new mechanism for non-exosomal secretion of tau protein PLoS One 2014 9 e100760 10.1371/journal.pone.0100760 24971751 PMC4074092 · DOI
  13. [18]Dujardin S Colin M Buee L Invited review: animal models of tauopathies and their implications for research/translation into the clinic Neuropathol Appl Neurobiol 2015 41 59 80 10.1111/nan.12200 25428793 · DOI
  14. [19]Dujardin S Lecolle K Caillierez R Begard S Zommer N Lachaud C Carrier S Dufour N Auregan G Winderickx J Hantraye P Deglon N Colin M Buee L Neuron-to-neuron wild-type tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies Acta Neuropathol Commun 2014 2 14 10.1186/2051-5960-2-14 24479894 PMC3922636 · DOI
  15. [20]Falcon B Cavallini A Angers R Glover S Murray TK Barnham L Jackson S O'Neill MJ Isaacs AM Hutton ML Szekeres PG Goedert M Bose S Conformation determines the seeding potencies of native and recombinant tau aggregates J Biol Chem 2015 290 1049 1065 10.1074/jbc.M114.589309 25406315 PMC4294473 · DOI
  16. [21]Forrest Shelley L Kril Jillian J Halliday Glenda M Reply: Will FTLD-tau work for all when FTDP-17 retires? Brain 2018 141 8 e63 e63 10.1093/brain/awy179 29947744 · DOI
  17. [23]Ghetti B Oblak AL Boeve BF Johnson KA Dickerson BC Goedert M Invited review: frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging Neuropathol Appl Neurobiol 2015 41 24 46 10.1111/nan.12213 25556536 PMC4329416 · DOI
  18. [24]Giannakopoulos P Herrmann FR Bussiere T Bouras C Kovari E Perl DP Morrison JH Gold G Hof PR Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease Neurology 2003 60 1495 1500 10.1212/01.WNL.0000063311.58879.01 12743238 · DOI · Paper page
  19. [25]Goedert M The ordered assembly of tau is the gain-of-toxic function that causes human tauopathies Alzheimers Dement 2016 12 1040 1050 10.1016/j.jalz.2016.09.001 27686274 · DOI
  20. [26]Grundke-Iqbal I Iqbal K Quinlan M Tung YC Zaidi MS Wisniewski HM Microtubule-associated protein tau. A component of Alzheimer paired helical filaments J Biol Chem 1986 261 6084 6089 3084478
  21. [27]Hasegawa M Smith MJ Goedert M Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly FEBS Lett 1998 437 207 210 10.1016/S0014-5793(98)01217-4 9824291 · DOI
  22. [28]Himmler A Drechsel D Kirschner MW Martin DWJ Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains Mol Cell Biol 1989 9 1381 1388 10.1128/MCB.9.4.1381 2498649 PMC362554 · DOI
  23. [29]Holmes BB Furman JL Mahan TE Yamasaki TR Mirbaha H Eades WC Belaygorod L Cairns NJ Holtzman DM Diamond MI Proteopathic tau seeding predicts tauopathy in vivo Proc Natl Acad Sci U S A 2014 111 E4376 E4385 10.1073/pnas.1411649111 25261551 PMC4205609 · DOI · Paper page
  24. [30]Hoover BR Reed MN Su J Penrod RD Kotilinek LA Grant MK Pitstick R Carlson GA Lanier LM Yuan LL Ashe KH Liao D Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration Neuron 2010 68 1067 1081 10.1016/j.neuron.2010.11.030 21172610 PMC3026458 · DOI · Paper page
  25. [31]Hottinger AF Azzouz M Deglon N Aebischer P Zurn AD Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus J Neurosci 2000 20 5587 5593 10.1523/JNEUROSCI.20-15-05587.2000 10908595 PMC6772542 · DOI
  26. [33]Irwin DJ Brettschneider J McMillan CT Cooper F Olm C Arnold SE Van Deerlin VM Seeley WW Miller BL Lee EB Lee VM Grossman M Trojanowski JQ Deep clinical and neuropathological phenotyping of pick disease Ann Neurol 2016 79 272 287 10.1002/ana.24559 26583316 PMC4755803 · DOI
  27. [34]Jeganathan S Hascher A Chinnathambi S Biernat J Mandelkow EM Mandelkow E Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of tau and generates a pathological (MC-1) conformation J Biol Chem 2008 283 32066 32076 10.1074/jbc.M805300200 18725412 · DOI · Paper page
  28. [35]Jicha GA Berenfeld B Davies P Sequence requirements for formation of conformational variants of tau similar to those found in Alzheimer's disease J Neurosci Res 1999 55 713 723 10.1002/(SICI)1097-4547(19990315)55:6<713::AID-JNR6>3.0.CO;2-G 10220112 · DOI
  29. [36]Jicha GA Bowser R Kazam IG Davies P Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau J Neurosci Res 1997 48 128 132 10.1002/(SICI)1097-4547(19970415)48:2<128::AID-JNR5>3.0.CO;2-E 9130141 · DOI
  30. [37]Karch CM Jeng AT Goate AM Extracellular tau levels are influenced by variability in tau that is associated with tauopathies J Biol Chem 2012 287 42751 42762 10.1074/jbc.M112.380642 23105105 PMC3522274 · DOI
  31. [38]Katsinelos T Zeitler M Dimou E Karakatsani A Muller HM Nachman E Steringer JP Ruiz de Almodovar C Nickel W Jahn TR Unconventional secretion mediates the trans-cellular spreading of tau Cell Rep 2018 23 2039 2055 10.1016/j.celrep.2018.04.056 29768203 · DOI
  32. [39]Kovacs GG Invited review: neuropathology of tauopathies: principles and practice Neuropathol Appl Neurobiol 2015 41 3 23 10.1111/nan.12208 25495175 · DOI · Paper page
  33. [40]Li X Kumar Y Zempel H Mandelkow EM Biernat J Mandelkow E Novel diffusion barrier for axonal retention of tau in neurons and its failure in neurodegeneration EMBO J 2011 30 4825 4837 10.1038/emboj.2011.376 22009197 PMC3243615 · DOI
  34. [41]Liu L Drouet V Wu JW Witter MP Small SA Clelland C Duff K Trans-synaptic spread of tau pathology in vivo PLoS One 2012 7 e31302 10.1371/journal.pone.0031302 22312444 PMC3270029 · DOI
  35. [42]Malia TJ Teplyakov A Ernst R Wu SJ Lacy ER Liu X Vandermeeren M Mercken M Luo J Sweet RW Gilliland GL Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti-tau antibody AT8 Proteins 2016 84 427 434 10.1002/prot.24988 26800003 PMC5067699 · DOI
  36. [43]Maurage CA Sergeant N Ruchoux MM Hauw JJ Delacourte A Phosphorylated serine 199 of microtubule-associated protein tau is a neuronal epitope abundantly expressed in youth and an early marker of tau pathology Acta Neuropathol 2003 105 89 97 10.1007/s00401-002-0608-7 12536218 · DOI · Paper page
  37. [44]Mercken M Vandermeeren M Lubke U Six J Boons J Van de Voorde A Martin JJ Gheuens J Monoclonal antibodies with selective specificity for Alzheimer tau are directed against phosphatase-sensitive epitopes Acta Neuropathol 1992 84 265 272 10.1007/BF00227819 1384266 · DOI
  38. [45]Mirbaha H, Chen D, Morazova OA, Ruff KM, Sharma AM, Liu X, Goodarzi M, Pappu RV, Colby DW, Mirzaei H, Joachimiak LA, Diamond MI (2018) Inert and seed-competent tau monomers suggest structural origins of aggregation. Elife 7. 10.7554/eLife.36584 PMC6039173 29988016 · DOI
  39. [46]Mocanu MM Nissen A Eckermann K Khlistunova I Biernat J Drexler D Petrova O Schonig K Bujard H Mandelkow E Zhou L Rune G Mandelkow EM The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous tau in inducible mouse models of tauopathy J Neurosci 2008 28 737 748 10.1523/JNEUROSCI.2824-07.2008 18199773 PMC6670355 · DOI · Paper page
  40. [47]Mohamed NV Plouffe V Remillard-Labrosse G Planel E Leclerc N Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons Sci Rep 2014 4 5715 10.1038/srep05715 25030297 PMC4101526 · DOI
  41. [48]Mudher A Colin M Dujardin S Medina M Dewachter I Alavi Naini SM Mandelkow EM Mandelkow E Buee L Goedert M Brion JP What is the evidence that tau pathology spreads through prion-like propagation? Acta Neuropathol Commun 2017 5 99 10.1186/s40478-017-0488-7 29258615 PMC5735872 · DOI · Paper page
  42. [50]Plouffe V Mohamed NV Rivest-McGraw J Bertrand J Lauzon M Leclerc N Hyperphosphorylation and cleavage at D421 enhance tau secretion PLoS One 2012 7 e36873 10.1371/journal.pone.0036873 22615831 PMC3352936 · DOI
  43. [51]Polydoro M Dzhala VI Pooler AM Nicholls SB McKinney AP Sanchez L Pitstick R Carlson GA Staley KJ Spires-Jones TL Hyman BT Soluble pathological tau in the entorhinal cortex leads to presynaptic deficits in an early Alzheimer's disease model Acta Neuropathol 2014 127 257 270 10.1007/s00401-013-1215-5 24271788 PMC3946978 · DOI · Paper page
  44. [52]Pooler AM Phillips EC Lau DH Noble W Hanger DP Physiological release of endogenous tau is stimulated by neuronal activity EMBO Rep 2013 14 389 394 10.1038/embor.2013.15 23412472 PMC3615658 · DOI · Paper page
  45. [53]Porzig R Singer D Hoffmann R Epitope mapping of mAbs AT8 and Tau5 directed against hyperphosphorylated regions of the human tau protein Biochem Biophys Res Commun 2007 358 644 649 10.1016/j.bbrc.2007.04.187 17499212 · DOI
  46. [54]Rosseels J Van den Brande J Violet M Jacobs D Grognet P Lopez J Huvent I Caldara M Swinnen E Papegaey A Caillierez R Buee-Scherrer V Engelborghs S Lippens G Colin M Buee L Galas MC Vanmechelen E Winderickx J Tau monoclonal antibody generation based on humanized yeast models: impact on tau oligomerization and diagnostics J Biol Chem 2015 290 4059 4074 10.1074/jbc.M114.627919 25540200 PMC4326816 · DOI
  47. [55]Saito Y Ruberu NN Sawabe M Arai T Tanaka N Kakuta Y Yamanouchi H Murayama S Staging of argyrophilic grains: an age-associated tauopathy J Neuropathol Exp Neurol 2004 63 911 918 10.1093/jnen/63.9.911 15453090 · DOI
  48. [57]Sanders DW Kaufman SK DeVos SL Sharma AM Mirbaha H Li A Barker SJ Foley AC Thorpe JR Serpell LC Miller TM Grinberg LT Seeley WW Diamond MI Distinct tau prion strains propagate in cells and mice and define different tauopathies Neuron 2014 82 1271 1288 10.1016/j.neuron.2014.04.047 24857020 PMC4171396 · DOI · Paper page
  49. [58]Santa-Maria I Varghese M Ksiezak-Reding H Dzhun A Wang J Pasinetti GM Paired helical filaments from Alzheimer disease brain induce intracellular accumulation of tau protein in aggresomes J Biol Chem 2012 287 20522 20533 10.1074/jbc.M111.323279 22496370 PMC3370237 · DOI
  50. [59]Schweers O Mandelkow EM Biernat J Mandelkow E Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments Proc Natl Acad Sci U S A 1995 92 8463 8467 10.1073/pnas.92.18.8463 7667312 PMC41177 · DOI
  51. [61]Simic G Babic Leko M Wray S Harrington C Delalle I Jovanov-Milosevic N Bazadona D Buee L de Silva R Di Giovanni G Wischik C Hof PR Tau protein hyperphosphorylation and aggregation in Alzheimer's disease and other Tauopathies, and possible neuroprotective strategies Biomolecules 2016 6 6 10.3390/biom6010006 26751493 PMC4808800 · DOI
  52. [62]Simon D Garcia-Garcia E Royo F Falcon-Perez JM Avila J Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles FEBS Lett 2012 586 47 54 10.1016/j.febslet.2011.11.022 22138183 · DOI
  53. [64]Tang Z Ioja E Bereczki E Hultenby K Li C Guan Z Winblad B Pei JJ mTor mediates tau localization and secretion: implication for Alzheimer's disease Biochim Biophys Acta 2015 1853 1646 1657 10.1016/j.bbamcr.2015.03.003 25791428 · DOI · Paper page
  54. [65]Tardivel M Begard S Bousset L Dujardin S Coens A Melki R Buee L Colin M Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological tau protein assemblies Acta Neuropathol Commun 2016 4 117 10.1186/s40478-016-0386-4 27809932 PMC5096005 · DOI · Paper page
  55. [66]Verny M Jellinger KA Hauw JJ Bancher C Litvan I Agid Y Progressive supranuclear palsy: a clinicopathological study of 21 cases Acta Neuropathol 1996 91 427 431 10.1007/s004010050446 8928621 · DOI
  56. [67]von Bergen M Barghorn S Biernat J Mandelkow EM Mandelkow E Tau aggregation is driven by a transition from random coil to beta sheet structure Biochim Biophys Acta 2005 1739 158 166 10.1016/j.bbadis.2004.09.010 15615635 · DOI
  57. [68]von Bergen M Barghorn S Li L Marx A Biernat J Mandelkow EM Mandelkow E Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure J Biol Chem 2001 276 48165 48174 10.1074/jbc.M105196200 11606569 · DOI
  58. [69]Williams DR Holton JL Strand C Pittman A de Silva R Lees AJ Revesz T Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson's syndrome Brain 2007 130 1566 1576 10.1093/brain/awm104 17525140 · DOI
  59. [70]Yamada K Holth JK Liao F Stewart FR Mahan TE Jiang H Cirrito JR Patel TK Hochgrafe K Mandelkow EM Holtzman DM Neuronal activity regulates extracellular tau in vivo J Exp Med 2014 211 387 393 10.1084/jem.20131685 24534188 PMC3949564 · DOI

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Authors
Dujardin, S., Bégard, S., Caillierez, R., Lachaud, C., Carrier, S., Lieger, S., Gonzalez, J. A., Deramecourt, V., Déglon, N., Maurage, C.-A., Frosch, M. P., Hyman, B. T., Colin, M., & Buée, L.
Affiliations
  • Harvard University (US)
  • Inserm (FR)
  • Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author
  • Colin, Morvane
  • Buée, Luc
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2018-11-29
Volume
6
Issue
1
Pages
132-132
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-018-0637-7
PMC
PMC6263555
OpenAlex
W2902279935
Cited by
109
References
71
Citations by year
2026: 8 · 2025: 13 · 2024: 10 · 2023: 12 · 2022: 6 · 2021: 24 · 2020: 16 · 2019: 20
FWCI
10.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by)
  • IRIS (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agence Nationale de la Recherche (LabEx Distalz, SpreadTau)
  • National Institutes of Health (P50 AG005134)
  • dn2M (VicTaur)
  • Association France Alzheimer (n/a)
  • CNRS (n/a)
  • Fondation Plan Alzheimer (n/a)
  • Alzheimer's association (2018-AARF-591935)
  • National Institute on Aging (P50 AG005134)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
Keywords
tauopathy, tau isoforms, MAPT mutations, tau propagation, tau misfolding, tau hyperphosphorylation, Alzheimer's disease, cell-to-cell transmission, tau aggregation
MeSH terms
Adult, Aged, Aged, 80 and over, Animals, Brain, Disease Models, Animal, Female, Humans, Injections, Intraventricular, Male, Middle Aged, Mutation, Phosphorylation, Severity of Illness Index, tau Proteins, Rats, Wistar, Disease Progression, Protein Isoforms, Tauopathies, Rats, Proteostasis Deficiencies

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