Tau physiology and pathomechanisms in frontotemporal lobar degeneration

Journal of Neurochemistry

Volumn , Issue , 2016, Pages 71-94

  Bodea, Liviu Gabriel ^a   Eckert, Anne ^b   Ittner, Lars Matthias ^c   Piguet, Olivier ^d   Götz, Jürgen ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b UNIVERSITY OF BASEL   (Switzerland)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

^d NEUROSCIENCE RESEARCH AUSTRALIA   (Australia)

Author keywords

microtubule; phosphorylation; post translational; spreading; synapse; transgenic

Indexed keywords

MICROTUBULE ASSOCIATED PROTEIN; TAU PROTEIN;

CELL COMPARTMENTALIZATION; CELL CYCLE; DENDRITIC SPINE; EPIGENETICS; FAMILIAL DISEASE; FRONTOTEMPORAL DEMENTIA; GENE; GENE MUTATION; GENETIC ORGANIZATION; GENETIC TRANSCRIPTION; HUMAN; MAPT GENE; MEMBRANE STABILIZATION; MICROTUBULE; NERVE CELL DEGENERATION; NERVE FIBER TRANSPORT; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; REVIEW; SYNAPSE; TAUOPATHY;

EID: 84981186452     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.13600     Document Type: Review

References (267)

1. Ahmed Z., Bigio E. H., Budka H. et al. (2013) Globular glial tauopathies (GGT): consensus recommendations. Acta Neuropathol. 126, 537–544.
2. Alavi Naini S. M. and Soussi-Yanicostas N. (2015) Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies?. Oxid. Med. Cell. Longev. 2015, 151979.
3. Allen B., Ingram E., Takao M. et al. (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J. Neurosci. 22, 9340–9351.
4. Alonso A. C., Grundke-Iqbal I. and Iqbal K. (1996) Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med. 2, 783–787.
5. Alzheimer A. (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allg. Z Psychiat. 64, 146–148.
6. Alzheimer A. (1911) Über eigenartige Krankheitsfälle des späteren Alters. Z ges Neurol Psychiat 4, 356–385.
7. Amadoro G., Corsetti V., Florenzano F. et al. (2014) AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons. Neurobiol. Dis. 62, 489–507.
8. Andorfer C. (2005) Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human Tau isoforms. J. Neurosci. 25, 5446–5454.
9. Andorfer C., Kress Y., Espinoza M., Silva R., De Tucker K. L., Barde Y. A., Duff K. and Davies P. (2003) Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J. Neurochem. 86, 582–590.
10. Arendt T., Stieler J., Strijkstra A. M., Hut R. A., Rüdiger J., Van der Zee E. A., Harkany T., Holzer M. and Härtig W. (2003) Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J. Neurosci. 23, 6972–6981.
11. Arnold C. S., Johnson G. V., Cole R. N., Dong D. L., Lee M. and Hart G. W. (1996) The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine. J. Biol. Chem. 271, 28741–28744.
12. Asai H., Ikezu S., Tsunoda S., Medalla M., Luebke J., Haydar T., Wolozin B., Butovsky O., Kügler S. and Ikezu T. (2015) Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci. 18, 1584–1593.
13. Avila J. (2009) The tau code. Front. Aging Neurosci. 1, 1.
14. Bai Q., Garver J. A., Hukriede N. A. and Burton E. A. (2007) Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic Acids Res. 35, 6501–6516.
15. Baker M., Litvan I., Houlden H., Adamson J., Dickson D., Perez-Tur J., Hardy J., Lynch T., Bigio E. and Hutton M. (1999) Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum. Mol. Genet. 8, 711–715.
16. Ballatore C., Lee V. M.-Y. and Trojanowski J. Q. (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat. Rev. Neurosci. 8, 663–672.
17. Bancher C., Brunner C., Lassmann H., Budka H., Jellinger K., Wiche G., Seitelberger F., Grundke-Iqbal I., Iqbal K. and Wisniewski H. M. (1989) Accumulation of abnormally phosphorylated τ precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res. 477, 90–99.
18. Bhaskar K., Yen S.-H. and Lee G. (2005) Disease-related modifications in tau affect the interaction between Fyn and tau. J. Biol. Chem. 280, 35119–35125.
19. Black M. M., Slaughter T., Moshiach S., Obrocka M. and Fischer I. (1996) Tau is enriched on dynamic microtubules in the distal region of growing axons. J. Neurosci. 16, 3601–3619.
20. Bodea L.-G., Wang Y., Linnartz-Gerlach B. et al. (2014) Neurodegeneration by activation of the microglial complement-phagosome pathway. J. Neurosci. 34, 8546–8556.
21. Boehm J. (2013) A “danse macabre”: tau and Fyn in STEP with amyloid beta to facilitate induction of synaptic depression and excitotoxicity. Eur. J. Neurosci. 37, 1925–1930.
22. Bolkan B. J. and Kretzschmar D. (2014) Loss of tau results in defects in photoreceptor development and progressive neuronal degeneration in drosophila. Dev. Neurobiol. 74, 1210–1225.
23. Bouleau S. and Tricoire H. (2015) Drosophila models of Alzheimer's disease: advances, limits, and perspectives. J. Alzheimers Dis. 45, 1015–1038.
24. Boyne L. J., Tessler A., Murray M. and Fischer I. (1995) Distribution of Big tau in the central nervous system of the adult and developing rat. J. Comp. Neurol. 358, 279–293.
25. Braak H. and Del Tredici K.(2011) Alzheimer's pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol. 121, 589–595.
26. Brandt R., Léger J. and 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.
27. Brettschneider J., Tredici K., Del Lee V. M.-Y. and Trojanowski J. Q. (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat. Rev. Neurosci. 16, 109–120.
28. Buée L., Bussière T., Buée-Scherrer V., Delacourte A. and Hof P. R. (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Brain Res. Rev. 33, 95–130.
29. Butzlaff M., Hannan S. B., Karsten P. et al. (2015) Impaired retrograde transport by the Dynein/Dynactin complex contributes to Tau-induced toxicity. Hum. Mol. Genet. 24, 3623–3637.
30. Caceres A. and Kosik K. S. (1990) Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons. Nature 343, 461–463.
31. Cairns N. J., Bigio E. H., Mackenzie I. R. A. et al. (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol. 114, 5–22.
32. Calahorro F. and Ruiz-Rubio M. (2011) Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson's disease, Alzheimer's disease and autism spectrum disorder. Invertebr. Neurosci. 11, 73–83.
33. Cantero J. L., Hita-Yañez E., Moreno-Lopez B., Portillo F., Rubio A. and Avila J. (2010a) Tau protein role in sleep-wake cycle. J. Alzheimers Dis. 21, 411–421.
34. Cantero J. L., Moreno-Lopez B., Portillo F., Rubio A., Hita-Yañez E. and Avila J. (2011) Role of tau protein on neocortical and hippocampal oscillatory patterns. Hippocampus 21, 827–834.
35. Chatterjee S., Sang T.-K., Lawless G. M. and Jackson G. R. (2008) Dissociation of tau toxicity and phosphorylation: role of GSK-3, MARK and Cdk5 in a Drosophila model. Hum. Mol. Genet. 18, 164–177.
36. Chen J., Kanai Y., Cowan N. J. and Hirokawa N. (1992) Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons. Nature 360, 674–677.
37. Chen X., Li Y., Huang J., Cao D., Yang G., Liu W., Lu H. and Guo A. (2007) Study of tauopathies by comparing Drosophila and human tau in Drosophila. Cell Tissue Res. 329, 169–178.
38. Chen M., Martins R. N. and Lardelli M. (2009) Complex splicing and neural expression of duplicated tau genes in zebrafish embryos. J. Alzheimers Dis. 18, 305–317.
39. Chew Y. L., Fan X., Götz J. and Nicholas H. R. (2013) PTL-1 regulates neuronal integrity and lifespan in C. elegans. J. Cell Sci. 126, 2079–2091.
40. Chew Y. L., Götz J. and Nicholas H. R. (2015) Neuronal protein with tau-like repeats (PTL-1) regulates intestinal SKN-1 nuclear accumulation in response to oxidative stress. Aging Cell 14, 148–151.
41. Clavaguera F., Bolmont T., Crowther R. A. et al. (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat. Cell Biol. 11, 909–913.
42. Clavaguera F., Akatsu H., Fraser G. et al. (2013) Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc. Natl Acad. Sci. 110, 9535–9540.
43. Clavaguera F., Hench J., Lavenir I., Schweighauser G., Frank S., Goedert M. and Tolnay M. (2014) Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice. Acta Neuropathol. 127, 299–301.
44. Costa A. P., Tramontina A. C., Biasibetti R., Batassini C., Lopes M. W., Wartchow K. M., Bernardi C., Tortorelli L. S., Leal R. B. and Gonçalves C.-A. (2012) Neuroglial alterations in rats submitted to the okadaic acid-induced model of dementia. Behav. Brain Res. 226, 420–427.
45. Couchie D., Mavilia C., Georgieff I. S., Liem R. K., Shelanski M. L. and Nunez J. (1992) Primary structure of high molecular weight tau present in the peripheral nervous system. Proc. Natl Acad. Sci. USA 89, 4378–4381.
46. Cripps D., Thomas S. N., Jeng Y., Yang F., Davies P. and Yang A. J. (2006) Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J. Biol. Chem. 281, 10825–10838.
47. Cruchaga C., Vidal-Taboada J. M., Ezquerra M., Lorenzo E., Martinez-Lage P., Blazquez M., Tolosa E. and Pastor P. (2009) 5’-Upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration. Neurobiol. Dis. 33, 164–170.
48. Dabir D. V., Robinson M. B., Swanson E., Zhang B., Trojanowski J. Q., Lee V. M.-Y. and Forman M. S. (2006) Impaired glutamate transport in a mouse model of tau pathology in astrocytes. J. Neurosci. 26, 644–654.
49. David D. C., Hauptmann S., Scherping I. et al. (2005) Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. J. Biol. Chem. 280, 23802–23814.
50. Dawson H. N., Ferreira a., Eyster M. V., Ghoshal N., Binder L. I. and Vitek M. P. (2001) Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J. Cell Sci. 114, 1179–1187.
51. Dehmelt L. and Halpain S. (2005) The MAP2/tau family of microtubule-associated proteins. Genome Biol. 6, 204.
52. Delay J., Brion S. and Escourolle R. (1957) L'opposition anatomo-clinique des maladies de Pick et d'Alzheimer: Etude de 38 cas. Presse Med. 65, 1495–1497.
53. Deters N., Ittner L. M. and Götz J. (2009) Substrate-specific reduction of PP2A activity exaggerates tau pathology. Biochem. Biophys. Res. Commun. 379, 400–405.
54. Di Meco A., Joshi Y. B. and Praticò D. (2014) Sleep deprivation impairs memory, tau metabolism, and synaptic integrity of a mouse model of Alzheimer's disease with plaques and tangles. Neurobiol. Aging 35, 1813–1820.
55. Dixit R., Ross J. L., Goldman Y. E. and Holzbaur E. L. F. (2008) Differential regulation of dynein and kinesin motor proteins by tau. Science (80-.), 319, 1086–1089.
56. Doerflinger H., Benton R., Shulman J. M. and Johnston St D. (2003) The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium. Development 130, 3965–3975.
57. Dorval V. and Fraser P. E. (2006) Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and α-synuclein. J. Biol. Chem. 281, 9919–9924.
58. Drubin D. G., Caput D. and Kirschner M. W. (1984) Studies on the expression of the microtubule-associated protein, tau, during mouse brain development, with newly isolated complementary DNA probes. J. Cell Biol. 98, 1090–1097.
59. DuBoff B., Götz J. and Feany M. B. (2012) Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 75, 618–632.
60. Duff K., Knight H., Refolo L. M. et al. (2000) Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol. Dis. 7, 87–98.
61. Dujardin S., Colin M. and Buée L. (2015) Invited review: animal models of tauopathies and their implications for research/translation into the clinic. Neuropathol. Appl. Neurobiol. 41, 59–80.
62. Dumanchin C., Camuzat A., Campion D. et al. (1998) Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Hum. Mol. Genet. 7, 1825–1829.
63. Duyckaerts C., Braak H., Brion J.-P. et al. (2015) PART is part of Alzheimer disease. Acta Neuropathol. 129, 749–756.
64. Ebneth A., Godemann R., Stamer K., Illenberger S., Trinczek B. and Mandelkow E. (1998) Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease. J. Cell Biol. 143, 777–794.
65. Fanara P., Husted K. H., Selle K., Wong P.-Y. A. P., Banerjee J., Brandt R. and Hellerstein M. K. (2010) Changes in microtubule turnover accompany synaptic plasticity and memory formation in response to contextual fear conditioning in mice. Neuroscience 168, 167–178.
66. Feany M. B. and Dickson D. W. (1995) Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am. J. Pathol. 146, 1388–1396.
67. Fischer D., Mukrasch M. D., Biernat J., Bibow S., Blackledge M., Griesinger C., Mandelkow E. and Zweckstetter M. (2009) Conformational changes specific for pseudophosphorylation at serine 262 selectively impair binding of tau to microtubules. Biochemistry 48, 10047–10055.
68. Frandemiche M. L., Seranno S., De Rush. T., Borel E., Elie A., Arnal I., Lanté F. and Buisson A. (2014) Activity-dependent tau protein translocation to excitatory synapse is disrupted by exposure to amyloid-beta oligomers. J. Neurosci. 34, 6084–6097.
69. Frost B., Hemberg M., Lewis J. and Feany M. B. (2014) Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366.
70. Fulga T. A., Elson-Schwab I., Khurana V., Steinhilb M. L., Spires T. L., Hyman B. T. and Feany M. B. (2007) Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat. Cell Biol. 9, 139–148.
71. Funk K. E., Thomas S. N., Schafer K. N., Cooper G. L., Liao Z., Clark D. J., Yang A. J. and Kuret J. (2014) Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity. Biochem. J. 462, 77–88.
72. Gärtner U., Janke C., Holzer M., Vanmechelen E. and Arendt T. (1998) Postmortem changes in the phosphorylation state of tau-protein in the rat brain. Neurobiol. Aging 19, 535–543.
73. Gauthier-Kemper A., Weissmann C., Golovyashkina N., Sebo-Lemke Z., Drewes G., Gerke V., Heinisch J. J. and Brandt R. (2011) The frontotemporal dementia mutation R406W blocks tau's interaction with the membrane in an annexin A2-dependent manner. J. Cell Biol. 192, 647–661.
74. Georgieff I. S., Liem R. K., Couchie D., Mavilia C., Nunez J. and Shelanski M. L. (1993) Expression of high molecular weight tau in the central and peripheral nervous systems. J. Cell Sci. 105 Pt 3, 729–737.
75. Ghetti B., Oblak A. L., Boeve B. F., Johnson K. A., Dickerson B. C. and Goedert M. (2015) Invited review: frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathol. Appl. Neurobiol. 41, 24–46.
76. Goedert M. (2015) Alzheimer's and Parkinson's diseases: the prion concept in relation to assembled Aβ, tau, and α-synuclein. Science 349, 1255555.
77. Goedert M. and Jakes R. (1990) Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J. 9, 4225–4230.
78. Goedert M., Wischik C. M., Crowther R. A., Walker J. E. and Klug A. (1988) Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc. Natl Acad. Sci. USA 85, 4051–4055.
79. Goedert M., Spillantini M. G., Potier M. C., Ulrich J. and 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.
80. Goedert M., Spillantini M. G., Cairns N. J. and Crowther R. A. (1992) Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8, 159–168.
81. Goedert M., Baur C. P., Ahringer J., Jakes R., Hasegawa M., Spillantini M. G., Smith M. J. and Hill F. (1996) PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J. Cell Sci. 109 Pt 1, 2661–2672.
82. Goedert M., Ghetti B. and Spillantini M. G. (2012) Frontotemporal dementia: implications for understanding Alzheimer disease. Cold Spring Harb. Perspect Med. 2, a006254.
83. Gómez-Isla T., Hollister R., West H., Mui S., Growdon J. H., Petersen R. C., Parisi J. E. and Hyman B. T. (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann. Neurol. 41, 17–24.
84. Gong C. X., Lidsky T., Wegiel J., Zuck L., Grundke-Iqbal I. and Iqbal K. (2000) Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. J. Biol. Chem. 275, 5535–5544.
85. Gonzalez C. (2013) Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nat. Rev. Cancer 13, 172–183.
86. Gordon P., Hingula L., Krasny M. L., Swienckowski J. L., Pokrywka N. J. and Raley-Susman K. M. (2008) The invertebrate microtubule-associated protein PTL-1 functions in mechanosensation and development in Caenorhabditis elegans. Dev. Genes. Evol. 218, 541–551.
87. Gorno-Tempini M. L., Hillis A. E., Weintraub S. et al. (2011) Classification of primary progressive aphasia and its variants. Neurology 76, 1006–1014.
88. Götz J. and Ittner L. M. (2008) Animal models of Alzheimer's disease and frontotemporal dementia. Nat. Rev. Neurosci. 9, 532–544.
89. Götz J., Probst A., Spillantini M. G., Schäfer T., Jakes R., Bürki K. and Goedert M. (1995) Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform. EMBO J. 14, 1304–1313.
90. Götz J., Chen F., Barmettler R. and Nitsch R. M. (2001a) Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem. 276, 529–534.
91. Götz J., Chen F., vanDorpe J. and Nitsch R. M. (2001b) Formation of neurofibrillary tangles in P301 l tau transgenic mice induced by Abeta 42 fibrils. Science 293, 1491–1495.
92. Götz J., Tolnay M., Barmettler R., Chen F., Probst A. and Nitsch R. M. (2001c) Oligodendroglial tau filament formation in transgenic mice expressing G272V tau. Eur. J. Neurosci. 13, 2131–2140.
93. Götz J., Eckert A., Matamales M., Ittner L. M. and Liu X. (2011) Modes of Aβ toxicity in Alzheimer's disease. Cell. Mol. Life Sci. 68, 3359–3375.
94. Grundke-Iqbal I., Iqbal K., Tung Y. C., Quinlan M., Wisniewski H. M. and Binder L. I. (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc. Natl Acad. Sci. USA 83, 4913–4917.
95. Haltiwanger R. S., Kelly W. G., Roquemore E. P., Blomberg M. A., Dong L., Kreppel L., Chou T. Y. and Hart G. W. (1992) Glycosylation of nuclear and cytoplasmic proteins is ubiquitous and dynamic. Biochem. Soc. Trans. 20, 264–269.
96. Hanover J. A. and Wang P. (2013) O-GlcNAc cycling shows neuroprotective potential in C. elegans models of neurodegenerative disease. Worm 2, e27043.
97. Harada A., Oguchi K., Okabe S., Kuno J., Terada S., Ohshima T., Sato-Yoshitake R., Takei Y., Noda T. and Hirokawa N. (1994) Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 369, 488–491.
98. Harris K. A., Oyler G. A., Doolittle G. M., Vincent I., Lehman R. A. W., Kincaid R. L. and Billingsley M. L. (1993) Okadiac acid induces hyperphosphorylated forms of tau protein in human brain slices. Ann. Neurol. 33, 77–87.
99. Harris J. A., Koyama A., Maeda S., Ho K., Devidze N., Dubal D. B., Yu G.-Q., Masliah E. and Mucke L. (2012) Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits. PLoS ONE 7, e45881.
100. Härtig W., Klein C., Brauer K., Schüppel K. F., Arendt T., Brückner G. and Bigl V. (2000) Abnormally phosphorylated protein tau in the cortex of aged individuals of various mammalian orders. Acta Neuropathol. 100, 305–312.
101. He H. J., Wang X. S., Pan R., Wang D. L., Liu M. N. and He R. Q. (2009) The proline-rich domain of tau plays a role in interactions with actin. BMC Cell Biol. 10, 81.
102. Heidary G. and Fortini M. E. (2001) Identification and characterization of the Drosophila tau homolog. Mech. Dev. 108, 171–178.
103. Herrup K. and Yang Y. (2007) Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat. Rev. Neurosci. 8, 368–378.
104. Higuchi M., Ishihara T., Zhang B., Hong M., Andreadis A., Trojanowski J. and Lee V. M.-Y. (2002) Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration. Neuron 35, 433–446.
105. Higuchi M., Zhang B., Forman M. S., Yoshiyama Y., Trojanowski J. Q. and Lee V. M.-Y. (2005) Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies. J. Neurosci. 25, 9434–9443.
106. Höglinger G. U., Melhem N. M., Dickson D. W. et al. (2011) Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699–705.
107. Holmes B. B., DeVos S. L., Kfoury N. et al. (2013) Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc. Natl Acad. Sci. 110, E3138–E3147.
108. Hoover B. R., Reed M. N., Su J. et al. (2010) Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68, 1067–1081.
109. Horiguchi T., Uryu K., Giasson B. I., Ischiropoulos H., LightFoot R., Bellmann C., Richter-Landsberg C., Lee V. M.-Y. and Trojanowski J. Q. (2003) Nitration of tau protein is linked to neurodegeneration in tauopathies. Am. J. Pathol. 163, 1021–1031.
110. Hunsberger H. C., Rudy C. C., Batten S. R., Gerhardt G. A. and Reed M. N. (2015) P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway. J. Neurochem. 132, 169–182.
111. Hutton M., Lendon C. L., Rizzu P. et al. (1998) Association of missense and 5’-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702–705.
112. Iba M., Guo J. L., McBride J. D., Zhang B., Trojanowski J. Q. and Lee V. M.-Y. (2013) Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic Mouse model of Alzheimer's-like tauopathy. J. Neurosci. 33, 1024–1037.
113. Ikeda M., Kawarai T., Kawarabayashi T. et al. (2005) Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. Am. J. Pathol. 166, 521–531.
114. Ikegami S., Harada A. and Hirokawa N. (2000) Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice. Neurosci. Lett. 279, 129–132.
115. Iqbal K., Wang X., Blanchard J., Liu F., Gong C.-X. and Grundke-Iqbal I. (2010) Alzheimer's disease neurofibrillary degeneration: pivotal and multifactorial. Biochem. Soc. Trans. 38, 962–966.
116. Irwin D. J., Cairns N. J., Grossman M., McMillan C. T., Lee E. B., Deerlin V. M., Van Lee. V. M.-Y. and Trojanowski J. Q. (2015) Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine. Acta Neuropathol. 129, 469–491.
117. Ischiropoulos H. and Al-Mehdi A. B. (1995) Peroxynitrite-mediated oxidative protein modifications. FEBS Lett. 364, 279–282.
118. Ishihara T., Hong M., Zhang B., Nakagawa Y., Lee M. K., Trojanowski J. Q. and Lee V. M. (1999) Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24, 751–762.
119. Ishihara T., Higuchi M., Zhang B., Yoshiyama Y., Hong M., Trojanowski J. Q. and Lee V. M. (2001a) Attenuated neurodegenerative disease phenotype in tau transgenic mouse lacking neurofilaments. J. Neurosci. 21, 6026–6035.
120. Ishihara T., Zhang B., Higuchi M., Yoshiyama Y., Trojanowski J. Q. and Lee V. M. (2001b) Age-dependent induction of congophilic neurofibrillary tau inclusions in tau transgenic mice. Am. J. Pathol. 158, 555–562.
121. Ittner L. M., Ke Y. D. and Götz J. (2009) Phosphorylated tau interacts with c-Jun N-terminal kinase-interacting protein 1 (JIP1) in Alzheimer disease. J. Biol. Chem. 284, 20909–20916.
122. Ittner L. M., Ke Y. D. et al. (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 142, 387–397.
123. Ittner L. M., Halliday G. M., Kril J. J., Götz J., Hodges J. R. and Kiernan M. C. (2015) FTD and ALS—translating mouse studies into clinical trials. Nat. Rev. Neurol. 11, 360–366.
124. Jack C. R., Knopman D. S., Jagust W. J. et al. (2013) Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 12, 207–216.
125. Jackson G. R., Wiedau-Pazos M., Sang T. K., Wagle N., Brown C. a., Massachi S. and Geschwind D. H. (2002) Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron 34, 509–519.
126. Janning D., Igaev M., Sündermann F., Brühmann J., Beutel O., Heinisch J. J., Bakota L., Piehler J., Junge W. and Brandt R. (2014) Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons. Mol. Biol. Cell 25, 3541–3551.
127. Jaworski T., Dewachter I., Lechat B. et al. (2009) AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice. PLoS ONE 4, e7280.
128. Jho Y. S., Zhulina E. B., Kim M. W. and Pincus P. A. (2010) Monte carlo simulations of tau proteins: effect of phosphorylation. Biophys. J. 99, 2387–2397.
129. Kamat P. K., Rai S., Swarnkar S., Shukla R. and Nath C. (2014) Molecular and cellular mechanism of okadaic acid (OKA)-induced neurotoxicity: a novel tool for Alzheimer's disease therapeutic application. Mol. Neurobiol. 50, 852–865.
130. Kampers T., Pangalos M., Geerts H., Wiech H. and Mandelkow E. (1999) Assembly of paired helical filaments from mouse tau: implications for the neurofibrillary pathology in transgenic mouse models for Alzheimer's disease. FEBS Lett. 451, 39–44.
131. Kar S., Fan J., Smith M. J., Goedert M. and Amos L. A. (2003) Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. EMBO J. 22, 70–77.
132. Ke Y., Dramiga J., Schütz U., Kril J. J., Ittner L. M., Schröder H. and Götz J. (2012) Tau-mediated nuclear depletion and cytoplasmic accumulation of SFPQ in Alzheimer's and Pick's disease. PLoS ONE 7, e35678.
133. Khurana V., Merlo P., Duboff B., Fulga T. a., Sharp K. A., Campbell S. D., Götz J. and Feany M. B. (2012) A neuroprotective role for the DNA damage checkpoint in tauopathy. Aging Cell 11, 360–362.
134. Kim Y. H., Choi S. H., D'Avanzo C. et al. (2015) A 3D human neural cell culture system for modeling Alzheimer's disease. Nat. Protoc. 10, 985–1006.
135. Kimura T., Fukuda T., Sahara N. et al. (2010) Aggregation of detergent-insoluble tau is involved in neuronal loss but not in synaptic loss. J. Biol. Chem. 285, 38692–38699.
136. Kins S., Crameri A., Evans D. R. H., Hemmings B. A., Nitsch R. M. and Götz J. (2001) Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. J. Biol. Chem. 276, 38193–38200.
137. Klein C., Kramer E.-M., Cardine A.-M., Schraven B., Brandt R. and Trotter J. (2002) Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau. J. Neurosci. 22, 698–707.
138. Klein R. L., Lin W.-L., Dickson D. W., Lewis J., Hutton M., Duff K., Meyer E. M. and King M. A. (2004) Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau. Am. J. Pathol. 164, 347–353.
139. Konzack S., Thies E., Marx A., Mandelkow E.-M. and Mandelkow E. (2007) Swimming against the tide: mobility of the microtubule-associated protein tau in neurons. J. Neurosci. 27, 9916–9927.
140. Kopeikina K. J., Polydoro M., Tai H. C., Yaeger E., Carlson G. a., Pitstick R., Hyman B. T. and Spires-Jones T. L. (2013) Synaptic alterations in the rTg4510 mouse model of tauopathy. J. Comp. Neurol. 521, 1334–1353.
141. Kosik K. S., Joachim C. L. and Selkoe D. J. (1986) Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc. Natl Acad. Sci. USA 83, 4044–4048.
142. Kosik K. S., Orecchio L. D., Bakalis S. and Neve R. L. (1989) Developmentally regulated expression of specific tau sequences. Neuron 2, 1389–1397.
143. Kosmidis S., Grammenoudi S., Papanikolopoulou K. and Skoulakis E. M. C. (2010) Differential effects of tau on the integrity and function of neurons essential for learning in drosophila. J. Neurosci. 30, 464–477.
144. Kouri N., Whitwell J. L., Josephs K. A., Rademakers R. and Dickson D. W. (2011) Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat. Rev. Neurol. 7, 263–272.
145. Kovacs G. G., Majtenyi K., Spina S. et al. (2008) White matter tauopathy with globular glial inclusions: a distinct sporadic frontotemporal lobar degeneration. J. Neuropathol. Exp. Neurol. 67, 963–975.
146. Kraemer B. C., Zhang B., Leverenz J. B., Thomas J. H., Trojanowski J. Q. and Schellenberg G. D. (2003) Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc. Natl Acad. Sci. USA 100, 9980–9985.
147. Krstic D., Madhusudan A., Doehner J. et al. (2012) Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J. Neuroinflammation 9, 151.
148. Kumar S., Tepper K., Kaniyappan S., Biernat J., Wegmann S., Mandelkow E. M., Müller D. J. and Mandelkow E. (2014) Stages and conformations of the tau repeat domain during aggregation and its effect on neuronal toxicity. J. Biol. Chem. 289, 20318–20332.
149. Kunze A., Meissner R., Brando S., Renaud P. (2011) Co-pathological connected primary neurons in a microfluidic device for Alzheimer studies. Biotechnol. Bioeng. 108, 2241–2245.
150. Kuret J., Congdon E. E., Li G., Yin H., Yu X. and Zhong Q. (2005) Evaluating triggers and enhancers of tau fibrillization. Microsc. Res. Tech. 67, 141–155.
151. Lannuzel A., Michel P., Höglinger G. and Champy P. (2003) The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism. Neuroscience 121, 287–296.
152. Lasagna-Reeves C. A., Castillo-Carranza D. L., Sengupta U., Clos A. L., Jackson G. R. and Kayed R. (2011) Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice. Mol. Neurodegener. 6, 39.
153. Ledesma M. D., Bonay P. and Avila J. (1995) Tau protein from Alzheimer's disease patients is glycated at its tubulin-binding domain. J. Neurochem. 65, 1658–1664.
154. Lee G., Cowan N. and Kirschner M. (1988) The primary structure and heterogeneity of tau protein from mouse brain. Science 239, 285–288.
155. Lee G., Newman S. T., Gard D. L., Band H. and Panchamoorthy G. (1998) Tau interacts with src-family non-receptor tyrosine kinases. J. Cell Sci. 111 Pt 2, 3167–3177.
156. Lee V. M., Goedert M. and Trojanowski J. Q. (2001) Neurodegenerative auopathies. Annu. Rev. Neurosci. 24, 1121–1159.
157. Lee V. M.-Y., Brunden K. R., Hutton M. and Trojanowski J. Q. (2011) Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets. Cold Spring Harb. Perspect Med. 1, a006437.
158. Lei P., Ayton S., Finkelstein D. I. et al. (2012) Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat. Med. 18, 291–295.
159. Leroy K., Ando K., Laporte V. et al. (2012) Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice. Am. J. Pathol. 181, 1928–1940.
160. Lewis J., McGowan E., Rockwood J. et al. (2000) Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25, 402–405.
161. Lewis J., Dickson D. W., Lin W. L. et al. (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293, 1487–1491.
162. Li H.-L., Wang H.-H., Liu S.-J., Deng Y.-Q., Zhang Y.-J., Tian Q., Wang X.-C. et al. (2007) Phosphorylation of tau antagonizes apoptosis by stabilizing beta-catenin, a mechanism involved in Alzheimer’s neurodegeneration. Proc. Natl. Acad. Sci. U. S. A. 104, 3591–3596.
163. Li X., Kumar Y., Zempel H., Mandelkow E.-M., Biernat J. and Mandelkow E. (2011) Novel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration. EMBO J. 30, 4825–4837.
164. Li J., Liu D., Sun L., Lu Y. and Zhang Z. (2012a) Advanced glycation end products and neurodegenerative diseases: mechanisms and perspective. J. Neurol. Sci. 317, 1–5.
165. Li X.-H., Lv B.-L., Xie J.-Z., Liu J., Zhou X.-W. and Wang J.-Z. (2012b) AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation. Neurobiol. Aging 33, 1400–1410.
166. Lim F., Hernández F., Lucas J. J., Gómez-Ramos P., Morán M. a. and Avila J. (2001) FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and Tau filaments in forebrain. Mol. Cell Neurosci. 18, 702–714.
167. Lin W., Gao L. and Chen X. (2015) Protein-Specific Imaging of O-GlcNAcylation in Single Cells. Chem. Bio. Chem. 16, 2571–2575.
168. Liu C. and Götz J. (2013) Profiling murine tau with 0N, 1N and 2N isoform-specific antibodies in brain and peripheral organs reveals distinct subcellular localization, with the 1N isoform being enriched in the nucleus. PLoS ONE 8, 1–18.
169. LoPresti P., Szuchet S., Papasozomenos S. C., Zinkowski R. P. and Binder L. I. (1995) Functional implications for the microtubule-associated protein tau: localization in oligodendrocytes. Proc. Natl Acad. Sci. USA 92, 10369–10373.
170. Ma Q.-L., Zuo X., Yang F. et al. (2014) Loss of MAP function leads to hippocampal synapse loss and deficits in the Morris Water Maze with aging. J. Neurosci. 34, 7124–7136.
171. Mackenzie I. R. A., Neumann M., Bigio E. H. et al. (2010) Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol. 119, 1–4.
172. Mandelkow E.-M. and Mandelkow E. (2012) Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb. Perspect Med. 2, a006247.
173. Maphis N., Xu G., Kokiko-Cochran O. N., Jiang S., Cardona A., Ransohoff R. M., Lamb B. T. and Bhaskar K. (2015) Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain 138, 1738–1755.
174. Maurin H., Chong S.-A., Kraev I. et al. (2014) Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. PLoS ONE 9, e87605.
175. McDermott J. B., Aamodt S. and Aamodt E. (1996) ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins. Biochemistry 35, 9415–9423.
176. Medina M. and Avila J. (2015) Further understanding of tau phosphorylation: implications for therapy. Expert Rev. Neurother. 15, 115–122.
177. Medina M., Avila J. and Villanueva N. (2013) Use of okadaic acid to identify relevant phosphoepitopes in pathology: a focus on neurodegeneration. Mar. Drugs 11, 1656–1668.
178. Merino-Serrais P., Benavides-Piccione R., Blazquez-Llorca L., Kastanauskaite A., Rábano A., Avila J. and DeFelipe J. (2013) The influence of phospho-τ on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease. Brain 136, 1913–1928.
179. Mertens J., Stüber K., Poppe D., Doerr J., Ladewig J., Brüstle O. and Koch P. (2013) Embryonic stem cell-based modeling of tau pathology in human neurons. Am. J. Pathol. 182, 1769–1779.
180. Min S.-W., Cho S.-H., Zhou Y. et al. (2010) Acetylation of tau inhibits Its degradation and contributes to tauopathy. Neuron 67, 953–966.
181. Mondragón-Rodríguez S., Trillaud-Doppia E., Dudilot A., Bourgeois C., Lauzon M., Leclerc N. and Boehm J. (2012) Interaction of endogenous tau protein with synaptic proteins is regulated by N-methyl-D-aspartate receptor-dependent tau phosphorylation. J. Biol. Chem. 287, 32040–32053.
182. Moraga D. M., Nuñez P., Garrido J. and Maccioni R. B. (1993) A tau fragment containing a repetitive sequence induces bundling of actin filaments. J. Neurochem. 61, 979–986.
183. Morishima-Kawashima M., Hasegawa M., Takio K., Suzuki M., Yoshida H., Titani K. and Ihara Y. (1995) Proline-directed and non-proline-directed phosphorylation of PHF-tau. J. Biol. Chem. 270, 823–829.
184. Morris M., Maeda S., Vossel K. and Mucke L. (2011) The many faces of tau. Neuron 70, 410–426.
185. Morris M., Hamto P., Adame A., Devidze N., Masliah E. and Mucke L. (2013) Age-appropriate cognition and subtle dopamine-independent motor deficits in aged Tau knockout mice. Neurobiol. Aging 34, 1523–1529.
186. Morris M., Knudsen G. M., Maeda S., Trinidad J. C., Ioanoviciu A., Burlingame A. L. and Mucke L. (2015) Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. Nat. Neurosci. 18, 1183–1189.
187. Morsch R., Simon W. and Coleman P. D. (1999) Neurons may live for decades with neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 58, 188–197.
188. Murrell J. R., Koller D., Foroud T., Goedert M., Spillantini M. G., Edenberg H. J., Farlow M. R. and Ghetti B. (1997) Familial multiple-system tauopathy with presenile dementia is localized to chromosome 17. Am. J. Hum. Genet. 61, 1131–1138.
189. Nelson P. T. and Saper C. B. (1996) Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50 immunoreactive dystrophic neurites in the cerebral cortex of sheep. Neurosci. Lett. 208, 77–80.
190. Nishimura I., Yang Y. and Lu B. (2004) PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 116, 671–682.
191. Oddo S., Caccamo A., Shepherd J. D., Murphy M. P., Golde T. E., Kayed R., Metherate R., Mattson M. P., Akbari Y. and LaFerla F. M. (2003) Triple-transgenic model of Alzheimer's Disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39, 409–421.
192. Paquet D., Bhat R., Sydow A. et al. (2009) Technical advance A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J. Clin. Invest. 119, 1382–1395.
193. Pick A. (1892) Ueber die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager med Wschr 17, 165–167.
194. Polanco J. C. and Götz J. (2015) No full admission for tau to the exclusive prion club yet. EMBO J., 1–3.
195. Polydoro M., Acker C. M., Duff K., Castillo P. E. and Davies P. (2009) Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J. Neurosci. 29, 10741–10749.
196. Poorkaj P., Bird T. D., Wijsman E., Nemens E., Garruto R. M., Anderson L., Andreadis A., Wiederholt W. C., Raskind M. and Schellenberg G. D. (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815–825.
197. Pountney D., Huang Y., Burns R., Haan E., Thompson P., Blumbergs P. and Gai W. (2003) SUMO-1 marks the nuclear inclusions in familial neuronal intranuclear inclusion disease. Exp. Neurol. 184, 436–446.
198. Probst A., Götz J., Wiederhold K. H. et al. (2000) Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol. 99, 469–481.
199. Rascovsky K., Hodges J. R., Knopman D. et al. (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134, 2456–2477.
200. Reyes J. F., Geula C., Vana L. and Binder L. I. (2012) Selective tau tyrosine nitration in non-AD tauopathies. Acta Neuropathol. 123, 119–132.
201. Rhein V., Song X., Wiesner A. et al. (2009) Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proc. Natl Acad. Sci. USA 106, 20057–20062.
202. Roberson E. D., Scearce-Levie K., Palop J. J., Yan F., Cheng I. H., Wu T., Gerstein H., Yu G.-Q. and Mucke L. (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 316, 750–754.
203. Rosenberg K. J., Ross J. L., Feinstein H. E., Feinstein S. C. and Israelachvili J. (2008) Complementary dimerization of microtubule-associated tau protein: implications for microtubule bundling and tau-mediated pathogenesis. Proc. Natl Acad. Sci. USA 105, 7445–7450.
204. Rosenmann H., Grigoriadis N., Karussis D., Boimel M., Touloumi O., Ovadia H. and Abramsky O. (2006) Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Arch. Neurol. 63, 1459–1467.
205. Rozenstein-Tsalkovich L., Grigoriadis N., Lourbopoulos A., Nousiopoulou E., Kassis I., Abramsky O., Karussis D. and Rosenmann H. (2013) Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation. Exp. Neurol. 248, 451–456.
206. Saito Y., Ruberu N. N., Sawabe M., Arai T., Tanaka N., Kakuta Y., Yamanouchi H. and Murayama S. (2004) Staging of argyrophilic grains: an age-associated tauopathy. J. Neuropathol. Exp. Neurol. 63, 911–918.
207. Saito T., Matsuba Y., Mihira N., Takano J., Nilsson P., Itohara S., Iwata N. and Saido T. C. (2014) Single App knock-in mouse models of Alzheimer's disease. Nat. Neurosci. 17, 661–663.
208. Sanders D. W., Kaufman S. K., DeVos S. L. et al. (2014) Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82, 1271–1288.
209. SantaCruz K., Lewis J., Spires T. et al. (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309, 476–81.
210. Santarella R. A., Skiniotis G., Goldie K. N., Tittmann P., Gross H., Mandelkow E. M., Mandelkow E. and Hoenger A. (2004) Surface-decoration of microtubules by human tau. J. Mol. Biol. 339, 539–553.
211. Sapir T., Frotscher M., Levy T., Mandelkow E.-M. and Reiner O. (2012) Tau's role in the developing brain: implications for intellectual disability. Hum. Mol. Genet. 21, 1681–1692.
212. Scattoni M. L., Gasparini L., Alleva E., Goedert M., Calamandrei G. and Spillantini M. G. (2010) Early behavioural markers of disease in P301S tau transgenic mice. Behav. Brain Res. 208, 250–257.
213. Schultz C., Hubbard G. B., Rüb U., Braak E. and Braak H. (2000) Age-related progression of tau pathology in brains of baboons. Neurobiol. Aging 21, 905–912.
214. Schweers O., Mandelkow E. M., Biernat J. and Mandelkow E. (1995) 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. USA 92, 8463–8467.
215. Semenova I., Burakov A., Berardone N., Zaliapin I., Slepchenko B., Svitkina T., Kashina A. and Rodionov V. (2008) Actin dynamics is essential for myosin-based transport of membrane organelles. Curr. Biol. 18, 1581–1586.
216. Sennvik K., Boekhoorn K., Lasrado R. et al. (2007) Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice. FASEB J. 21, 2149–2161.
217. Sharma V. M., Litersky J. M., Bhaskar K. and Lee G. (2007) Tau impacts on growth-factor-stimulated actin remodeling. J. Cell Sci. 120, 748–757.
218. Shipton O. A., Leitz J. R., Dworzak J. et al. (2011) Tau protein is required for amyloid -induced impairment of hippocampal long-term potentiation. J. Neurosci. 31, 1688–1692.
219. Sperfeld A D., Collatz M. B., Baier H. et al. (1999) FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann. Neurol. 46, 708–715.
220. Spillantini M. G. and Goedert M. (2013) Tau pathology and neurodegeneration. Lancet Neurol. 12, 609–622.
221. Spillantini M. G., Crowther R. A., Kamphorst W., Heutink P. and vanSwieten J. C. (1998a) Tau pathology in two dutch families with mutations in the microtubule-binding region of tau. Am. J. Pathol. 153, 1359–1363.
222. Spillantini M. G., Murrell J. R., Goedert M., Farlow M. R., Klug A. and Ghetti B. (1998b) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl Acad. Sci. USA 95, 7737–7741.
223. Stefansson H., Helgason A., Thorleifsson G. et al. (2005) A common inversion under selection in Europeans. Nat. Genet. 37, 129–137.
224. Steinhilb M. L., Dias-Santagata D., Fulga T. A., Felch D. L. and Feany M. B. (2007) Tau phosphorylation sites work in concert to promote neurotoxicity in vivo. Mol. Biol. Cell 18, 5060–5068.
225. Sun M. and Chen L. (2015) Studying tauopathies in Drosophila: a fruitful model. Exp. Neurol. 274, 52–57.
226. Sundar P. D., Yu C.-E., Sieh W. et al. (2006) Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia. Hum. Mol. Genet. 16, 295–306.
227. Takahashi K., Ishida M., Komano H. and Takahashi H. (2008) SUMO-1 immunoreactivity co-localizes with phospho-Tau in APP transgenic mice but not in mutant tau transgenic mice. Neurosci. Lett. 441, 90–93.
228. Takashima A. (2013) Tauopathies and tau oligomers. J. Alzheimer's Dis. 37, 565–568.
229. Takei Y., Teng J., Harada A. and Hirokawa N. (2000) Defects axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J. Cell Biol. 150, 989–1000.
230. Takeuchi H., Iba M., Inoue H. et al. (2011) P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating. PLoS ONE 6, e21050.
231. Tanaka E. M. and Kirschner M. W. (1991) Microtubule behavior in the growth cones of living neurons during axon elongation. J. Cell Biol. 115, 345–363.
232. Tanemura K., Akagi T., Murayama M. et al. (2001) Formation of filamentous tau aggregations in transgenic mice expressing V337M human tau. Neurobiol. Dis. 8, 1036–1045.
233. Tatebayashi Y., Miyasaka T., Chui D.-H. et al. (2002) Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tau. Proc. Natl Acad. Sci. USA 99, 13896–13901.
234. Tell V. and Hilgeroth A. (2013) Recent developments of protein kinase inhibitors as potential AD therapeutics. Front. Cell. Neurosci. 7, 189.
235. Tepper K., Biernat J., Kumar S., Wegmann S., Timm T., Hübschmann S., Redecke L., Mandelkow E.-M., Müller D. J. and Mandelkow E. (2014) Oligomer formation of tau protein hyperphosphorylated in cells. J. Biol. Chem. 289, 34389–34407.
236. Tien N.-W., Wu G.-H., Hsu C.-C., Chang C.-Y. and Wagner O. I. (2011) Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor's motility characteristics in C. elegans neurons. Neurobiol. Dis. 43, 495–506.
237. Tomasiewicz H. G., Flaherty D. B., Soria J. P. and Wood J. G. (2002) Transgenic zebrafish model of neurodegeneration. J. Neurosci. Res. 70, 734–745.
238. Trinczek B., Ebneth A., Mandelkow E. M. and Mandelkow E. (1999) Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles. J. Cell Sci. 112 Pt 1, 2355–2367.
239. Tu S., Okamoto S.-I., Lipton S. A. and Xu H. (2014) Oligomeric Aβ-induced synaptic dysfunction in Alzheimer's disease. Mol. Neurodegener. 9, 1–12.
240. Tucker K. L., Meyer M. and Barde Y. A. (2001) Neurotrophins are required for nerve growth during development. Nat. Neurosci. 4, 29–37.
241. Umeda T., Yamashita T., Kimura T., Ohnishi K., Takuma H., Ozeki T., Takashima A., Tomiyama T. and Mori H. (2013) Neurodegenerative disorder FTDP-17-related tau intron 10 + 16C→T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice. Am. J. Pathol. 183, 211–225.
242. Umeda T., Maekawa S., Kimura T., Takashima A., Tomiyama T. and Mori H. (2014) Neurofibrillary tangle formation by introducing wild-type human tau into APP transgenic mice. Acta Neuropathol. 127, 685–698.
243. Usenovic M., Niroomand S., Drolet R. E., Yao L., Gaspar R. C., Hatcher N. G., Schachter J., Renger J. J. and Parmentier-Batteur S. (2015) Internalized tau oligomers cause neurodegeneration by inducing accumulation of pathogenic tau in human neurons derived from induced pluripotent stem cells. J. Neurosci. 35, 14234–14250.
244. Varki A. (2007) Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature 446, 1023–1029.
245. Vossel K. A., Zhang K., Brodbeck J., Daub A. C., Sharma P., Finkbeiner S., Cui B. and Mucke L. (2010) Tau reduction prevents Aß-induced defects in axonal transport. Science (80-.). 330, 198.
246. Wang Z., Udeshi N. D., O'Malley M., Shabanowitz J., Hunt D. F. and Hart G. W. (2010) Enrichment and site mapping of O-linked N-acetylglucosamine by a combination of chemical/enzymatic tagging, photochemical cleavage, and electron transfer dissociation mass spectrometry. Mol. Cell Proteomics 9, 153–160.
247. Warmus B. A., Sekar D. R., McCutchen E., Schellenberg G. D., Roberts R. C., McMahon L. L. and Roberson E. D. (2014) Tau-mediated NMDA receptor impairment underlies dysfunction of a selectively vulnerable network in a mouse model of frontotemporal dementia. J. Neurosci. 34, 16482–16495.
248. Wegmann S., Maury E. A., Kirk M. J. et al. (2015) Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. EMBO J. 34, 3028–3041.
249. Wei M. L. and Andreadis A. (1998) Splicing of a regulated exon reveals additional complexity in the axonal microtubule-associated protein tau. J. Neurochem. 70, 1346–1356.
250. Weingarten M. D., Lockwood A. H., Hwo S. Y. and Kirschner M. W. (1975) A protein factor essential for microtubule assembly. Proc. Natl Acad. Sci. USA 72, 1858–1862.
251. Wilhelmsen K. C., Lynch T., Pavlou E., Higgins M. and Nygaard T. G. (1994) Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21-22. Am. J. Hum. Genet. 55, 1159–1165.
252. Williams D. R., Holton J. L., Strand C., Pittman A., Silva R., De Lees. A. J. and Revesz T. (2007) Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson's syndrome. Brain 130, 1566–1576.
253. Wischik C. M., Novak M., Thøgersen H. C., Edwards P. C., Runswick M. J., Jakes R., Walker J. E., Milstein C., Roth M. and Klug A. (1988) Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc. Natl Acad. Sci. USA 85, 4506–4510.
254. Wittmann C. W., Wszolek M. F., Shulman J. M., Salvaterra P. M., Lewis J., Hutton M. and Feany M. B. (2001) Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293, 711–714.
255. Wood J. G., Mirra S. S., Pollock N. J. and Binder L. I. (1986) Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau). Proc. Natl Acad. Sci. USA 83, 4040–4043.
256. Xia D., Li C. and Götz J. (2015) Pseudophosphorylation of tau at distinct epitopes or the presence of the P301L mutation targets the microtubule-associated protein tau to dendritic spines. Biochim. Biophys. Acta 1852, 913–924.
257. Xie C., Miyasaka T., Yoshimura S., Hatsuta H., Yoshina S., Kage-Nakadai E., Mitani S., Murayama S. and Ihara Y. (2014) The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles. PLoS ONE 9, e89796.
258. Yang X. J. and Seto E. (2008) Lysine Acetylation: codified Crosstalk with Other Posttranslational Modifications. Mol. Cell 31, 449–461.
259. Yoshida M. (2014) Astrocytic inclusions in progressive supranuclear palsy and corticobasal degeneration. Neuropathology 34, 555–570.
260. Yoshiyama Y., Higuchi M., Zhang B., Huang S.-M., Iwata N., Saido T. C., Maeda J., Suhara T., Trojanowski J. Q. and Lee V. M.-Y. (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337–351.
261. Yuan A., Kumar A., Peterhoff C., Duff K. and Nixon R. A. (2008) Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice. J. Neurosci. 28, 1682–1687.
262. Yuzwa S. A., Yadav A. K., Skorobogatko Y., Clark T., Vosseller K. and Vocadlo D. J. (2011) Mapping O-GlcNAc modification sites on tau and generation of a site-specific O-GlcNAc tau antibody. Amino Acids 40, 857–868.
263. Yuzwa S. A., Shan X., Macauley M. S., Clark T., Skorobogatko Y., Vosseller K. and Vocadlo D. J. (2012) Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat. Chem. Biol. 8, 393–399.
264. van der Zee J. and Van Broeckhoven C. (2014) Dementia in 2013: frontotemporal lobar degeneration—building on breakthroughs. Nat. Rev. Neurol. 10, 70–72.
265. Zempel H. and Mandelkow E. (2014) Lost after translation: missorting of tau protein and consequences for Alzheimer disease. Trends Neurosci. 37, 721–732.
266. Zhang B., Higuchi M., Yoshiyama Y., Ishihara T., Forman M. S., Martinez D., Joyce S., Trojanowski J. Q. and Lee V. M.-Y. (2004) Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy. J. Neurosci. 24, 4657–4667.
267. Zmuda J. F. and Rivas R. J. (2000) Actin disruption alters the localization of tau in the growth cones of cerebellar granule neurons. J. Cell Sci. 113, 2797–2809.