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Linked References

1. K. A. Jellinger, “Alzheimer 100—highlights in the history of Alzheimer research,” Journal of Neural Transmission, vol. 113, no. 11, pp. 1603–1623, 2006. View at Publisher · View at Google Scholar · View at Scopus
2. S. W. Scheff, S. T. DeKosky, and D. A. Price, “Quantitative assessment of cortical synaptic density in Alzheimer's disease,” Neurobiology of Aging, vol. 11, no. 1, pp. 29–37, 1990. View at Publisher · View at Google Scholar · View at Scopus
3. S. W. Scheff and D. A. Price, “Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies,” Neurobiology of Aging, vol. 24, no. 8, pp. 1029–1046, 2003. View at Publisher · View at Google Scholar · View at Scopus
4. S. W. Scheff and D. A. Price, “Alzheimer's disease-related alterations in synaptic density: neocortex and hippocampus,” Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 101–115, 2006. View at Scopus
5. R. D. Terry, E. Masliah, D. P. Salmon et al., “Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment,” Annals of Neurology, vol. 30, no. 4, pp. 572–580, 1991. View at Publisher · View at Google Scholar · View at Scopus
6. J. Hardy and D. Allsop, “Amyloid deposition as the central event in the aetiology of Alzheimer's disease,” Trends in Pharmacological Sciences, vol. 12, no. 10, pp. 383–388, 1991. View at Publisher · View at Google Scholar · View at Scopus
7. J. A. Hardy and G. A. Higgins, “Alzheimer's disease: the amyloid cascade hypothesis,” Science, vol. 256, no. 5054, pp. 184–185, 1992. View at Scopus
8. J. Hardy, “Alzheimer's disease: the amyloid cascade hypothesis—an update and reappraisal,” Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 151–153, 2006. View at Scopus
9. C. Haass, M. G. Schlossmacher, A. Y. Hung et al., “Amyloid β-peptide is produced by cultured cells during normal metabolism,” Nature, vol. 359, no. 6393, pp. 322–325, 1992. View at Publisher · View at Google Scholar · View at Scopus
10. T. Vandebroek, T. Vanhelmont, D. Terwel et al., “Identification and isolation of a hyperphosphorylated, conformationally changed intermediate of human protein tau expressed in yeast,” Biochemistry, vol. 44, no. 34, pp. 11466–11475, 2005. View at Publisher · View at Google Scholar · View at Scopus
11. C. Menuet, P. Borghgraef, V. Matarazzo, et al., “Raphe tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: possible implications for tauopathies and Alzheimer's disease,” Respiratory Physiology & Neurobiology, vol. 178, no. 2, pp. 290–303, 2011.
12. R. E. Tanzi and L. Bertram, “Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective,” Cell, vol. 120, no. 4, pp. 545–555, 2005. View at Publisher · View at Google Scholar · View at Scopus
13. H. A. Archer, P. Edison, D. J. Brooks et al., “Amyloid load and cerebral atrophy in Alzheimer's disease: an 11C-PIB positron emission tomography study,” Annals of Neurology, vol. 60, no. 1, pp. 145–147, 2006. View at Publisher · View at Google Scholar · View at Scopus
14. Y. Li, J. O. Rinne, L. Mosconi et al., “Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer's disease,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 12, pp. 2169–2181, 2008. View at Publisher · View at Google Scholar · View at Scopus
15. M. Jin, N. Shepardson, T. Yang, G. Chen, D. Walsh, and D. J. Selkoe, “Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce tau hyperphosphorylation and neuritic degeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 14, pp. 5819–5824, 2011. View at Publisher · View at Google Scholar · View at Scopus
16. C. Duyckaerts, B. Delatour, and M. C. Potier, “Classification and basic pathology of Alzheimer disease,” Acta Neuropathologica, vol. 118, no. 1, pp. 5–36, 2009. View at Publisher · View at Google Scholar · View at Scopus
17. P. V. Arriagada, J. H. Growdon, E. T. Hedley-Whyte, and B. T. Hyman, “Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease,” Neurology, vol. 42, no. 3 I, pp. 631–639, 1992. View at Scopus
18. R. B. Maccioni, M. Lavados, M. Guillon, et al., “Anomalously phosphorylated tau and Aβ fragments in the CSF correlates with cognitive impairment in MCI subjects,” Neurobiology of Aging, vol. 27, no. 2, pp. 237–244, 2006. View at Publisher · View at Google Scholar
19. T. Jaworski, I. Dewachter, C. M. Seymour et al., “Alzheimer's disease: old problem, new views from transgenic and viral models,” Biochimica et Biophysica Acta, vol. 1802, no. 10, pp. 808–818, 2010. View at Publisher · View at Google Scholar · View at Scopus
20. A. Harada, K. Oguchi, S. Okabe et al., “Altered microtubule organization in small-calibre axons of mice lacking tau protein,” Nature, vol. 369, no. 6480, pp. 488–491, 1994. View at Publisher · View at Google Scholar · View at Scopus
21. L. N. Clark, P. Poorkaj, Z. Wszolek et al., “Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 22, pp. 13103–13107, 1998. View at Scopus
22. M. Goedert, R. A. Crowther, and M. G. Spillantini, “Tau mutations cause frontotemporal dementias,” Neuron, vol. 21, no. 5, pp. 955–958, 1998. View at Publisher · View at Google Scholar · View at Scopus
23. M. Hong, M. Hong, V. Zhukareva et al., “Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17,” Science, vol. 282, no. 5395, pp. 1914–1917, 1998. View at Scopus
24. M. Hutton, C. L. Lendon, P. Rizzu et al., “Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17,” Nature, vol. 393, no. 6686, pp. 702–705, 1998. View at Publisher · View at Google Scholar · View at Scopus
25. J. Z. Wang and F. Liu, “Microtubule-associated protein tau in development, degeneration and protection of neurons,” Progress in Neurobiology, vol. 85, no. 2, pp. 148–175, 2008. View at Publisher · View at Google Scholar · View at Scopus
26. T. F. Gendron and L. Petrucelli, “The role of tau in neurodegeneration,” Molecular Neurodegeneration, vol. 4, no. 1, article 13, 2009. View at Publisher · View at Google Scholar · View at Scopus
27. J. van Swieten and M. G. Spillantini, “Hereditary frontotemporal dementia caused by tau gene mutations,” Brain Pathology, vol. 17, no. 1, pp. 63–73, 2007. View at Publisher · View at Google Scholar · View at Scopus
28. J. Zhou, Q. Yu, and T. Zou, “Alternative splicing of exon 10 in the tau gene as a target for treatment of tauopathies,” BMC Neuroscience, vol. 9, supplement 2, article S10, 2008. View at Publisher · View at Google Scholar · View at Scopus
29. M. S. Wolfe, “Tau mutations in neurodegenerative diseases,” The Journal of Biological Chemistry, vol. 284, no. 10, pp. 6021–6025, 2009. View at Publisher · View at Google Scholar · View at Scopus
30. D. G. Drubin, D. Caput, and M. W. Kirschner, “Studies on the expression of the microtubule-associated protein, tau, during mouse brain development, with newly isolated complementary DNA probes,” Journal of Cell Biology, vol. 98, no. 3, pp. 1090–1097, 1984. View at Scopus
31. L. I. Binder, A. Frankfurter, and L. I. Rebhun, “The distribution of tau in the mammalian central nervous system,” Journal of Cell Biology, vol. 101, no. 4, pp. 1371–1378, 1985. View at Scopus
32. L. Buee and A. Delacourte, “Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease,” Brain Pathology, vol. 9, no. 4, pp. 681–693, 1999. View at Scopus
33. M. G. Spillantini and M. Goedert, “Tau protein pathology in neurodegenerative diseases,” Trends in Neurosciences, vol. 21, no. 10, pp. 428–433, 1998. View at Publisher · View at Google Scholar · View at Scopus
34. M. G. Spillantini, T. D. Bird, and B. Ghetti, “Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies,” Brain Pathology, vol. 8, no. 2, pp. 387–402, 1998. View at Scopus
35. A. M. Pittman, H. C. Fung, and R. de Silva, “Untangling the tau gene association with neurodegenerative disorders,” Human Molecular Genetics, vol. 15, no. 2, pp. R188–R195, 2006. View at Publisher · View at Google Scholar · View at Scopus
36. B. Trinczek, J. Biernat, K. Baumann, E. M. Mandelkow, and E. Mandelkow, “Domains of tau protein, differential phosphorylation, and dynamic instability of microtubules,” Molecular Biology of the Cell, vol. 6, no. 12, pp. 1887–1902, 1995. View at Scopus
37. G. B. Witman, D. W. Cleveland, M. D. Weingarten, and M. W. Kirschner, “Tubulin requires tau for growth into microtubule initiating sites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 73, no. 11, pp. 4070–4074, 1976. View at Scopus
38. S. Kar, J. Fan, M. J. Smith, M. Goedert, and L. A. Amos, “Repeat motifs of tau bind to the insides of microtubules in the absence of taxol,” The EMBO Journal, vol. 22, no. 1, pp. 70–77, 2003. View at Publisher · View at Google Scholar · View at Scopus
39. R. Dixit, J. L. Ross, Y. E. Goldman, and E. L. F. Holzbaur, “Differential regulation of dynein and kinesin motor proteins by tau,” Science, vol. 319, no. 5866, pp. 1086–1089, 2008. View at Publisher · View at Google Scholar · View at Scopus
40. L. M. Ittner, Y. D. Ke, F. Delerue et al., “Dendritic function of tau mediates amyloid-β toxicity in Alzheimer's disease mouse models,” Cell, vol. 142, no. 3, pp. 387–397, 2010. View at Publisher · View at Google Scholar · View at Scopus
41. C. J. Leugers and G. Lee, “Tau potentiates nerve growth factor-induced mitogen-activated protein kinase signaling and neurite initiation without a requirement for microtubule binding,” The Journal of Biological Chemistry, vol. 285, no. 25, pp. 19125–19134, 2010. View at Publisher · View at Google Scholar · View at Scopus
42. M. Morris, S. Maeda, K. Vossel, and L. Mucke, “The many faces of tau,” Neuron, vol. 70, no. 3, pp. 410–426, 2011. View at Publisher · View at Google Scholar · View at Scopus
43. K. Santacruz, J. Lewis, T. Spires et al., “Tau suppression in a neurodegenerative mouse model improves memory function,” Science, vol. 309, no. 5733, pp. 476–481, 2005. View at Publisher · View at Google Scholar · View at Scopus
44. C. Andorfer, C. M. Acker, Y. Kress, P. R. Hof, K. Duff, and P. Davies, “Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms,” Journal of Neuroscience, vol. 25, no. 22, pp. 5446–5454, 2005. View at Publisher · View at Google Scholar · View at Scopus
45. T. Gomez-Isla, R. Hollister, H. West et al., “Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease,” Annals of Neurology, vol. 41, no. 1, pp. 17–24, 1997. View at Publisher · View at Google Scholar · View at Scopus
46. E. D. Roberson, K. Scearce-Levie, J. J. Palop et al., “Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model,” Science, vol. 316, no. 5825, pp. 750–754, 2007. View at Publisher · View at Google Scholar · View at Scopus
47. T. Jaworski, I. Dewachter, B. Lechat et al., “AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice,” PLoS One, vol. 4, no. 10, Article ID e7280, 2009. View at Publisher · View at Google Scholar · View at Scopus
48. S. Feuillette, L. Miguel, T. Frebourg, D. Campion, and M. Lecourtois, “Drosophila models of human tauopathies indicate that tau protein toxicity in vivo is mediated by soluble cytosolic phosphorylated forms of the protein,” Journal of Neurochemistry, vol. 113, no. 4, pp. 895–903, 2010. View at Publisher · View at Google Scholar · View at Scopus
49. V. Dorval and P. E. Fraser, “Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and α-synuclein,” The Journal of Biological Chemistry, vol. 281, no. 15, pp. 9919–9924, 2006. View at Publisher · View at Google Scholar · View at Scopus
50. S. W. Min, S. H. Cho, Y. Zhou et al., “Acetylation of tau inhibits its degradation and contributes to tauopathy,” Neuron, vol. 67, no. 6, pp. 953–966, 2010. View at Publisher · View at Google Scholar · View at Scopus
51. M. D. Ledesma, M. Perez, C. Colaco, and J. Avila, “Tau glycation is involved in aggregation of the protein but not in the formation of filaments,” Cellular and Molecular Biology, vol. 44, no. 7, pp. 1111–1116, 1998. View at Scopus
52. M. Takahashi, Y. Tsujioka, T. Yamada et al., “Glycosylation of microtubule-associated protein tau in Alzheimer's disease brain,” Acta Neuropathologica, vol. 97, no. 6, pp. 635–641, 1999. View at Publisher · View at Google Scholar · View at Scopus
53. C. Conde and A. Caceres, “Microtubule assembly, organization and dynamics in axons and dendrites,” Nature Reviews Neuroscience, vol. 10, no. 5, pp. 319–332, 2009. View at Publisher · View at Google Scholar · View at Scopus
54. J. Gotz, F. Chen, J. van Dorpe, and R. M. Nitsch, “Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ 42 fibrils,” Science, vol. 293, no. 5534, pp. 1491–1495, 2001. View at Publisher · View at Google Scholar · View at Scopus
55. A. Ferrari, F. Hoerndli, T. Baechi, R. M. Nitsch, and J. Gotz, “β-Amyloid induces paired helical filament-like tau filaments in tissue culture,” The Journal of Biological Chemistry, vol. 278, no. 41, pp. 40162–40168, 2003. View at Publisher · View at Google Scholar · View at Scopus
56. I. Kelleher, C. Garwood, D. P. Hanger, B. H. Anderton, and W. Noble, “Kinase activities increase during the development of tauopathy in htau mice,” Journal of Neurochemistry, vol. 103, no. 6, pp. 2256–2267, 2007. View at Publisher · View at Google Scholar · View at Scopus
57. M. L. Steinhilb, D. Dias-Santagata, T. A. Fulga, D. L. Felch, and M. B. Feany, “Tau phosphorylation sites work in concert to promote neurotoxicity in vivo,” Molecular Biology of the Cell, vol. 18, no. 12, pp. 5060–5068, 2007. View at Publisher · View at Google Scholar · View at Scopus
58. Y. Yu, X. Run, Z. Liang et al., “Developmental regulation of tau phosphorylation, tau kinases, and tau phosphatases,” Journal of Neurochemistry, vol. 108, no. 6, pp. 1480–1494, 2009. View at Publisher · View at Google Scholar · View at Scopus
59. K. B. Storey, “Mammalian hibernation: transcriptional and translational controls,” Advances in Experimental Medicine and Biology, vol. 543, pp. 21–38, 2003. View at Scopus
60. J. T. Stieler, T. Bullmann, F. Kohl, et al., “The physiological link between metabolic rate depression and tau phosphorylation in mammalian hibernation,” PLoS One, vol. 6, no. 1, Article ID e14530, 2011.
61. W. Hartig, J. Stieler, A. S. Boerema et al., “Hibernation model of tau phosphorylation in hamsters: selective vulnerability of cholinergic basal forebrain neurons—implications for Alzheimer's disease,” European Journal of Neuroscience, vol. 25, no. 1, pp. 69–80, 2007. View at Publisher · View at Google Scholar · View at Scopus
62. T. Arendt, J. Stieler, A. M. Strijkstra et al., “Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals,” Journal of Neuroscience, vol. 23, no. 18, pp. 6972–6981, 2003. View at Scopus
63. M. Yanagisawa, E. Planel, K. Ishiguro, and S. C. Fujita, “Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer's disease,” The FEBS Letters, vol. 461, no. 3, pp. 329–333, 1999. View at Publisher · View at Google Scholar · View at Scopus
64. Y. Okawa, K. Ishiguro, and S. C. Fujita, “Stress-induced hyperphosphorylation of tau in the mouse brain,” The FEBS Letters, vol. 535, no. 1–3, pp. 183–189, 2003. View at Publisher · View at Google Scholar · View at Scopus
65. E. Planel, K. E. G. Richter, C. E. Nolan et al., “Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia,” Journal of Neuroscience, vol. 27, no. 12, pp. 3090–3097, 2007. View at Publisher · View at Google Scholar · View at Scopus
66. N. Bohnen, M. A. Warner, E. Kokmen, and L. T. Kurland, “Early and midlife exposure to anesthesia and age of onset of Alzheimer's disease,” International Journal of Neuroscience, vol. 77, no. 3-4, pp. 181–185, 1994. View at Scopus
67. I. Bone and M. Rosen, “Alzheimer's disease and anaesthesia,” Anaesthesia, vol. 55, no. 6, pp. 592–593, 2000. View at Publisher · View at Google Scholar · View at Scopus
68. E. Planel, T. Miyasaka, T. Launey et al., “Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer's disease,” Journal of Neuroscience, vol. 24, no. 10, pp. 2401–2411, 2004. View at Publisher · View at Google Scholar · View at Scopus
69. E. Planel, A. Bretteville, L. Liu et al., “Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia,” The FASEB Journal, vol. 23, no. 8, pp. 2595–2604, 2009. View at Publisher · View at Google Scholar · View at Scopus
70. C. Menuet, P. Borghgraef, N. Voituron, et al., “Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau.P301L mice: possible implication for neurodegenerative diseases,” Neurobiology of Disease, vol. 46, no. 1, pp. 234–243, 2012.
71. K. Leroy, Z. Yilmaz, and J. P. Brion, “Increased level of active GSK-3β in Alzheimer's disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration,” Neuropathology and Applied Neurobiology, vol. 33, no. 1, pp. 43–55, 2007. View at Publisher · View at Google Scholar · View at Scopus
72. A. Takashima, “GSK-3 is essential in the pathogenesis of Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 309–317, 2006. View at Scopus
73. K. Ishiguro, A. Shiratsuchi, S. Sato et al., “Glycogen synthase kinase 3β is identical to tau protein kinase I generating several epitopes of paired helical filaments,” The FEBS Letters, vol. 325, no. 3, pp. 167–172, 1993. View at Publisher · View at Google Scholar · View at Scopus
74. C. A. Rankin, Q. Sun, and T. C. Gamblin, “Pre-assembled tau filaments phosphorylated by GSK-3b form large tangle-like structures,” Neurobiology of Disease, vol. 31, no. 3, pp. 368–377, 2008. View at Publisher · View at Google Scholar · View at Scopus
75. J. S. Song and S. D. Yang, “Tau protein kinase I/GSK-3β/kinase FA in heparin phosphorylates tau on Ser199, Thr231, Ser235, Ser262, Ser369, and Ser400 sites phosphorylated in Alzheimer disease brain,” Journal of Protein Chemistry, vol. 14, no. 2, pp. 95–105, 1995. View at Scopus
76. T. Engel, J. J. Lucas, P. Gomez-Ramos, M. A. Moran, J. Avila, and F. Hernandez, “Cooexpression of FTDP-17 tau and GSK-3β in transgenic mice induce tau polymerization and neurodegeneration,” Neurobiology of Aging, vol. 27, no. 9, pp. 1258–1268, 2006.
77. D. Terwel, D. Muyllaert, I. Dewachter et al., “Amyloid activates GSK-3β to aggravate neuronal tauopathy in bigenic mice,” American Journal of Pathology, vol. 172, no. 3, pp. 786–798, 2008. View at Publisher · View at Google Scholar · View at Scopus
78. K. Spittaels, C. van den Haute, J. van Dorpe et al., “Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice,” The Journal of Biological Chemistry, vol. 275, no. 52, pp. 41340–41349, 2000. View at Publisher · View at Google Scholar · View at Scopus
79. S. Jeganathan, A. Hascher, S. Chinnathambi, J. Biernat, E. M. Mandelkow, and E. Mandelkow, “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,” The Journal of Biological Chemistry, vol. 283, no. 46, pp. 32066–32076, 2008. View at Publisher · View at Google Scholar · View at Scopus
80. S. C. Papasozomenos and L. I. Binder, “Phosphorylation determines two distinct species of tau in the central nervous system,” Cell motility and the cytoskeleton, vol. 8, no. 3, pp. 210–226, 1987. View at Scopus
81. C. G. Dotti, G. A. Banker, and L. I. Binder, “The expression and distribution of the microtubule-associated proteins tau and microtubule-associated protein 2 in hippocampal neurons in the rat in situ and in cell culture,” Neuroscience, vol. 23, no. 1, pp. 121–130, 1987. View at Scopus
82. N. Hirokawa, T. Funakoshi, R. Sato-Harada, and Y. Kanai, “Selective stabilization of tau in axons and microtubule-associated protein 2C in cell bodies and dendrites contributes to polarized localization of cytoskeletal proteins in mature neurons,” Journal of Cell Biology, vol. 132, no. 4, pp. 667–679, 1996. View at Publisher · View at Google Scholar · View at Scopus
83. S. Aronov, G. Aranda, L. Behar, and I. Ginzburg, “Axonal tau mRNA localization coincides with tau protein in living neuronal cells and depends on axonal targeting signal,” Journal of Neuroscience, vol. 21, no. 17, pp. 6577–6587, 2001. View at Scopus
84. K. S. Kosik and A. M. Krichevsky, “The message and the messenger: delivering RNA in neurons,” Science's STKE, vol. 2002, no. 126, article e16, 2002. View at Scopus
85. X. Li, Y. Kumar, H. Zempel, E. M. Mandelkow, J. Biernat, and E. Mandelkow, “Novel diffusion barrier for axonal retention of tau in neurons and its failure in neurodegeneration,” The EMBO Journal, vol. 30, no. 23, pp. 4825–4837, 2011.
86. W. Yu, J. Polepalli, D. Wagh, J. Rajadas, R. Malenka, and B. Lu, “A critical role for the PAR-1/MARK-tau axis in mediating the toxic effects of Aβ on synapses and dendritic spines,” Human Molecular Genetics, vol. 21, no. 6, pp. 1384–1390, 2011.
87. B. R. Hoover, M. N. Reed, J. Su et al., “Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration,” Neuron, vol. 68, no. 6, pp. 1067–1081, 2010. View at Publisher · View at Google Scholar · View at Scopus
88. J. Gotz, A. Gladbach, L. Pennanen et al., “Animal models reveal role for tau phosphorylation in human disease,” Biochimica et Biophysica Acta, vol. 1802, no. 10, pp. 860–871, 2010. View at Publisher · View at Google Scholar · View at Scopus
89. D. Terwel, R. Lasrado, J. Snauwaert et al., “Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice,” The Journal of Biological Chemistry, vol. 280, no. 5, pp. 3963–3973, 2005. View at Publisher · View at Google Scholar · View at Scopus
90. T. L. Spires, J. D. Orne, K. SantaCruz et al., “Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy,” American Journal of Pathology, vol. 168, no. 5, pp. 1598–1607, 2006. View at Publisher · View at Google Scholar · View at Scopus
91. Z. Berger, H. Roder, A. Hanna et al., “Accumulation of pathological tau species and memory loss in a conditional model of tauopathy,” Journal of Neuroscience, vol. 27, no. 14, pp. 3650–3662, 2007. View at Publisher · View at Google Scholar · View at Scopus
92. A. Kremer, J. V. Louis, T. Jaworski, and F. van Leuven, “GSK3 and Alzheimer's disease: facts and fiction...,” Frontiers in Molecular Neuroscience, vol. 4, article 17, 2011. View at Publisher · View at Google Scholar
93. J. Kuret, C. N. Chirita, E. E. Congdon et al., “Pathways of tau fibrillization,” Biochimica et Biophysica Acta, vol. 1739, no. 2, pp. 167–178, 2005. View at Publisher · View at Google Scholar · View at Scopus
94. S. Barghorn and E. Mandelkow, “Toward a unified scheme for the aggregation of tau into Alzheimer paired helical filaments,” Biochemistry, vol. 41, no. 50, pp. 14885–14896, 2002. View at Publisher · View at Google Scholar · View at Scopus
95. N. Sahara, S. Maeda, M. Murayama et al., “Assembly of two distinct dimers and higher-order oligomers from full-length tau,” European Journal of Neuroscience, vol. 25, no. 10, pp. 3020–3029, 2007. View at Publisher · View at Google Scholar · View at Scopus
96. A. Watanabe, W. K. Hong, N. Dohmae, K. Takio, M. Morishima-Kawashima, and Y. Ihara, “Molecular aging of tau: disulfide-independent aggregation and non-enzymatic degradation in vitro and in vivo,” Journal of Neurochemistry, vol. 90, no. 6, pp. 1302–1311, 2004. View at Publisher · View at Google Scholar · View at Scopus
97. K. R. Patterson, C. Remmers, Y. Fu et al., “Characterization of prefibrillar tau oligomers in vitro and in Alzheimer disease,” The Journal of Biological Chemistry, vol. 286, no. 26, pp. 23063–23076, 2011. View at Publisher · View at Google Scholar · View at Scopus
98. A. Schneider, J. Biernat, M. von Bergen, E. Mandelkow, and E. M. Mandelkow, “Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments,” Biochemistry, vol. 38, no. 12, pp. 3549–3558, 1999. View at Publisher · View at Google Scholar · View at Scopus
99. A. Sydow, A. van der Jeugd, F. Zheng et al., “Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic tau mutant,” Journal of Neuroscience, vol. 31, no. 7, pp. 2511–2525, 2011. View at Publisher · View at Google Scholar · View at Scopus
100. H. Braak and E. Braak, “Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections,” Brain Pathology, vol. 1, no. 3, pp. 213–216, 1991. View at Scopus
101. H. Braak and K. Del Tredici, “The pathological process underlying Alzheimer's disease in individuals under thirty,” Acta Neuropathologica, vol. 121, no. 2, pp. 171–181, 2011. View at Publisher · View at Google Scholar · View at Scopus
102. B. Frost, R. L. Jacks, and M. I. Diamond, “Propagation of tau misfolding from the outside to the inside of a cell,” The Journal of Biological Chemistry, vol. 284, no. 19, pp. 12845–12852, 2009. View at Publisher · View at Google Scholar · View at Scopus
103. F. Clavaguera, T. Bolmont, R. A. Crowther et al., “Transmission and spreading of tauopathy in transgenic mouse brain,” Nature Cell Biology, vol. 11, no. 7, pp. 909–913, 2009. View at Publisher · View at Google Scholar · View at Scopus
104. L. M. Ittner and J. Gotz, “Amyloid-β and tau—a toxic pas de deux in Alzheimer's disease,” Nature Reviews Neuroscience, vol. 12, no. 2, pp. 67–72, 2011. View at Publisher · View at Google Scholar · View at Scopus
105. A. de Calignon, M. Polydoro, M. Suarez-Calvet, et al., “Propagation of tau pathology in a model of early Alzheimer's disease,” Neuron, vol. 73, no. 4, pp. 685–697, 2012.
106. L. Liu, V. Drouet, J. W. Wu, et al., “Trans-synaptic spread of tau pathology in vivo,” PLoS One, vol. 7, no. 2, Article ID e31302, 2012.
107. C. Duyckaerts, M. C. Potier, and B. Delatour, “Alzheimer disease models and human neuropathology: similarities and differences,” Acta Neuropathologica, vol. 115, no. 1, pp. 5–38, 2008. View at Publisher · View at Google Scholar · View at Scopus
108. K. Spittaels, C. van den Haute, J. van Dorpe et al., “Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein,” American Journal of Pathology, vol. 155, no. 6, pp. 2153–2165, 1999. View at Scopus
109. A. Kremer, H. Maurin, D. Demedts, H. Devijver, P. Borghgraef, and F. van Leuven, “Early improved and late defective cognition is reflected by dendritic spines in Tau.P301L mice,” Journal of Neuroscience, vol. 31, no. 49, pp. 18036–18047, 2011.
110. M. Dutschmann, C. Menuet, G. M. Stettner et al., “Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain and ponto-medullary brainstem nuclei,” Journal of Neuroscience, vol. 30, no. 5, pp. 1810–1821, 2010. View at Publisher · View at Google Scholar · View at Scopus
111. C. Menuet, Y. Cazals, C. Gestreau, et al., “Age-related impairment of ultrasonic vocalization in Tau.P301L mice: possible implication for progressive language disorders,” PLoS One, vol. 6, no. 10, Article ID e25770, 2011.
112. K. Boekhoorn, D. Terwel, B. Biemans et al., “Improved long-term potentiation and memory in young Tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy,” Journal of Neuroscience, vol. 26, no. 13, pp. 3514–3523, 2006. View at Publisher · View at Google Scholar · View at Scopus
113. T. Jaworski, S. Kugler, and F. van Leuven, “Modeling of tau-mediated synaptic and neuronal degeneration in Alzheimer's disease,” International Journal of Alzheimer's Disease, vol. 2010, Article ID 573138, 10 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
114. K. Spittaels, C. van den Haute, J. van Dorpe et al., “Neonatal neuronal overexpression of glycogen synthase kinase-3β reduces brain size in transgenic mice,” Neuroscience, vol. 113, no. 4, pp. 797–808, 2002. View at Publisher · View at Google Scholar · View at Scopus
115. D. Moechars, I. Dewachter, K. Lorent et al., “Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain,” The Journal of Biological Chemistry, vol. 274, no. 10, pp. 6483–6492, 1999. View at Publisher · View at Google Scholar · View at Scopus
116. A. Kremer, H. Maurin, P. Borghgraef, et al., “Time-line of clinical and pathological defects of mice with amyloid and tau pathology: relations to dendritic spines and location of amyloid and protein tau,” in preparation, 2012.
117. D. Moechars, K. Lorent, and F. van Leuven, “Premature death in transgenic mice that overexpress a mutant amyloid precursor protein is preceded by severe neurodegeneration and apoptosis,” Neuroscience, vol. 91, no. 3, pp. 819–830, 1999. View at Publisher · View at Google Scholar · View at Scopus
118. D. Muyllaert, A. Kremer, T. Jaworski et al., “Glycogen synthase kinase-3β, or a link between amyloid and tau pathology?” Genes, Brain and Behavior, vol. 7, no. 1, pp. 57–66, 2008. View at Publisher · View at Google Scholar · View at Scopus
119. D. Muyllaert, D. Terwel, P. Borghgraef, H. Devijver, I. Dewachter, and F. van Leuven, “Transgenic mouse models for Alzheimer's disease: the role of GSK-3B in combined amyloid and tau-pathology,” Reviews of Neurology, vol. 162, no. 10, pp. 903–907, 2006.
120. K. A. Conway, S. J. Lee, J. C. Rochet, T. T. Ding, R. E. Williamson, and P. T. Lansbury Jr., “Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 2, pp. 571–576, 2000. View at Publisher · View at Google Scholar · View at Scopus
121. D. B. Freir, R. Fedriani, D. Scully, et al., “Aβ oligomers inhibit synapse remodelling necessary for memory consolidation,” Neurobiology of Aging, vol. 32, no. 12, pp. 2211–2218, 2011.
122. J. Legleiter, E. Mitchell, G. P. Lotz et al., “Mutant huntingtin fragments form oligomers in a polyglutamine length-dependent manner in vitro and in vivo,” The Journal of Biological Chemistry, vol. 285, no. 19, pp. 14777–14790, 2010. View at Publisher · View at Google Scholar · View at Scopus
123. V. Novitskaya, O. V. Bocharova, I. Bronstein, and I. V. Baskakov, “Amyloid fibrils of mammalian prion protein are highly toxic to cultured cells and primary neurons,” The Journal of Biological Chemistry, vol. 281, no. 19, pp. 13828–13836, 2006. View at Publisher · View at Google Scholar · View at Scopus
124. J. J. Kril, S. Patel, A. J. Harding, and G. M. Halliday, “Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation,” Acta Neuropathologica, vol. 103, no. 4, pp. 370–376, 2002. View at Publisher · View at Google Scholar · View at Scopus
125. A. B. Rocher, J. L. Crimins, J. M. Amatrudo et al., “Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs,” Experimental Neurology, vol. 223, no. 2, pp. 385–393, 2010. View at Publisher · View at Google Scholar · View at Scopus
126. J. Wentzell and D. Kretzschmar, “Alzheimer's disease and tauopathy studies in flies and worms,” Neurobiology of Disease, vol. 40, no. 1, pp. 21–28, 2010. View at Publisher · View at Google Scholar · View at Scopus
127. C. M. Cowan, M. A. Sealey, S. Quraishe, et al., “Modelling tauopathies in Drosophila: insights from the fruit fly,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 598157, 16 pages, 2011. View at Publisher · View at Google Scholar
128. E. E. Congdon and K. E. Duff, “Is tau aggregation toxic or protective?” Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 453–457, 2008. View at Scopus
129. A. D. C. Alonso, B. Li, I. Grundke-Iqbal, and K. Iqbal, “Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 23, pp. 8864–8869, 2006. View at Publisher · View at Google Scholar · View at Scopus
130. R. A. Bodner, T. F. Outeiro, S. Altmann et al., “Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 11, pp. 4246–4251, 2006. View at Publisher · View at Google Scholar · View at Scopus
131. C. A. Lasagna-Reeves, D. L. Castillo-Carranza, U. Sengupta, A. L. Clos, G. R. Jackson, and R. Kayed, “Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice,” Molecular Neurodegeneration, vol. 6, no. 1, article 39, 2011. View at Publisher · View at Google Scholar · View at Scopus
132. K. Papanikolopoulou, S. Kosmidis, S. Grammenoudi, and E. M. C. Skoulakis, “Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction,” Biochemical Society Transactions, vol. 38, no. 4, pp. 981–987, 2010. View at Publisher · View at Google Scholar · View at Scopus
133. T. Jaworski, B. Lechat, D. Demedts, et al., “Dendritic degeneration, neurovascular defects, and inflammation precede neuronal loss in a mouse model for tau-mediated neurodegeneration,” American Journal of Pathology, vol. 179, no. 4, pp. 2001–2015, 2011.
134. T. Jaworski, I. Dewachter, B. Lechat, et al., “GSK-3α/β kinases and amyloid production in vivo,” Nature, vol. 480, no. 7376, pp. E4–E5, 2011.