Tau protein isoforms, phosphorylation and role in neurodegenerative disorders11These authors contributed equally to this work.

1998, Molecular and biochemical markers of Alzheimer’s disease. the Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on aging working group, Neurobiol. Aging, 19, 109, 10.1016/S0197-4580(98)00022-0 Aamodt, 1984, Microtubule-associated proteins connect microtubules and neurofilaments in vitro, Biochemistry, 23, 6023, 10.1021/bi00320a019 Albert, 1974, The subcortical dementia of progressive supranuclear palsy, J. Neurol. Neurosurg. Psychiatry, 37, 121, 10.1136/jnnp.37.2.121 Andreadis, 1995, Relative exon affinities and suboptimal splice site signals lead to non-equivalence of two cassette exons, Nucleic Acids Res., 23, 3585, 10.1093/nar/23.17.3585 Andreadis, 1992, Structure and novel exons of the human tau gene, Biochemistry, 31, 10626, 10.1021/bi00158a027 Andreadis, 1996, A tau promoter region without neuronal specificity, J. Neurochem., 66, 2257, 10.1046/j.1471-4159.1996.66062257.x Andreasen, 1999, Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample, Neurology, 53, 1488, 10.1212/WNL.53.7.1488 Andreasen, 1999, Cerebrospinal fluid tau and beta42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment, Neurosci. Lett., 273, 5, 10.1016/S0304-3940(99)00617-5 Andreasen, 1998, Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer’s disease: a community based follow-up study, J. Neurol. Neurosurg. Psychiatry, 64, 298, 10.1136/jnnp.64.3.298 Appelt, 1997, The association of tissue transglutaminase with human recombinant tau results in the formation of insoluble filamentous structures, Brain Res., 745, 21, 10.1016/S0006-8993(96)01121-3 Arai, 1997, Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology, Biochem. Biophys. Res. Commun., 236, 262, 10.1006/bbrc.1997.6908 Arai, 1995, Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease, Ann. Neurol., 38, 649, 10.1002/ana.410380414 Arnold, 1996, The microtubule-associated protein tau is extensively modified with O- linked N-acetylglucosamine, J. Biol. Chem., 271, 28741, 10.1074/jbc.271.46.28741 Arnold, 1991, The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’s disease, Cereb. Cortex, 1, 103, 10.1093/cercor/1.1.103 Arrasate, 1997, Role of glycosaminoglycans in determining the helicity of paired helical filaments, Am. J. Pathol., 151, 1115 Auer, 1995, Paired helical filament tau (PHF-tau) in Niemann–Pick type C disease is similar to PHF-tau in Alzheimer’s disease, Acta Neuropathol., 90, 547, 10.1007/BF00318566 Baker, 1999, Association of an extended haplotype in the tau gene with progressive supranuclear palsy, Hum. Mol. Genet., 8, 711, 10.1093/hmg/8.4.711 Ball, 1977, Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study, Acta Neuropathol., 37, 111, 10.1007/BF00692056 Bancher, 1996, On the relationship between measles virus and Alzheimer neurofibrillary tangles in subacute sclerosing panencephalitis, Neurobiol. Aging, 17, 527, 10.1016/0197-4580(96)00069-3 Baudier, 1987, Phosphorylation of tau proteins to a state like that in Alzheimer’s brain is catalyzed by a calcium/calmodulin-dependent kinase and modulated by phospholipids, J. Biol. Chem., 262, 17577, 10.1016/S0021-9258(18)45420-8 Baumann, 1993, Abnormal Alzheimer-like phosphorylation of tau protein by cyclin-dependent kinases cdk2 and cdk5, FEBS Lett., 336, 417, 10.1016/0014-5793(93)80849-P Bennett, 1998, Direct genetic evidence for involvement of tau in progressive supranuclear palsy. European Study Group on Atypical Parkinsonism Consortium, Neurology, 51, 982, 10.1212/WNL.51.4.982 Benzing, 1995, Apolipoprotein E immunoreactivity within neurofibrillary tangles: relationship to Tau and PHF in Alzheimer’s disease, Exp. Neurol., 132, 162, 10.1016/0014-4886(95)90021-7 Bergeron, 1997, Cortical degeneration in progressive supranuclear palsy. A comparison with cortical-basal ganglionic degeneration, J. Neuropathol. Exp. Neurol., 56, 726, 10.1097/00005072-199706000-00010 Bierer, 1995, Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer’s disease, Arch. Neurol., 52, 81, 10.1001/archneur.1995.00540250089017 Biernat, 1993, Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding, Neuron, 11, 153, 10.1016/0896-6273(93)90279-Z Bigio, 1999, Progressive supranuclear palsy with dementia: cortical pathology, J. Neuropathol. Exp. Neurol., 58, 359, 10.1097/00005072-199904000-00006 Binder, 1985, The distribution of tau in the mammalian central nervous system, J. Cell Biol., 101, 1371, 10.1083/jcb.101.4.1371 Bird, 1997, Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD, Neurology, 48, 949, 10.1212/WNL.48.4.949 Blennow, 1998, Combination of the different biological markers for increasing specificity of in vivo Alzheimer’s testing, J. Neural. Transm. Suppl., 53, 223, 10.1007/978-3-7091-6467-9_20 Blennow, 1995, Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?, Mol. Chem. Neuropathol., 26, 231, 10.1007/BF02815140 Bohm, 1990, Effect of MAP1, MAP2, and tau proteins on structural parameters of tubulin assemblies, Acta Histochem. Suppl., 39, 357 Bonifati, 1999, The tau gene in progressive supranuclear palsy: exclusion of mutations in coding exons and exon 10 splice sites, and identification of a new intronic variant of the disease-associated H1 haplotype in Italian cases, Neurosci. Lett., 274, 61, 10.1016/S0304-3940(99)00669-2 Bouras, 1994, Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital, Cereb. Cortex, 4, 138, 10.1093/cercor/4.2.138 Bouras, 1993, Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes, Neurosci. Lett., 153, 131, 10.1016/0304-3940(93)90305-5 Braak, 1997, Alzheimer’s disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon’s horn, Acta Neuropathol., 93, 323, 10.1007/s004010050622 Braak, 1985, On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer’s disease, Acta Neuropathol., 68, 325, 10.1007/BF00690836 Braak, 1991, Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections, Brain Pathol., 1, 213, 10.1111/j.1750-3639.1991.tb00661.x Braak, 1991, Neuropathological stageing of Alzheimer-related changes, Acta Neuropathol., 82, 239, 10.1007/BF00308809 Brady, 1995, Presence of tau in isolated nuclei from human brain, Neurobiol. Aging, 16, 479, 10.1016/0197-4580(95)00023-8 Bramblett, 1993, Abnormal tau phosphorylation at Ser396 in Alzheimer’s disease recapitulates development and contributes to reduced microtubule binding, Neuron, 10, 1089, 10.1016/0896-6273(93)90057-X Brandt, 1993, The balance between tau protein’s microtubule growth and nucleation activities: implications for the formation of axonal microtubules, J. Neurochem., 61, 997, 10.1111/j.1471-4159.1993.tb03613.x Brandt, 1995, Interaction of tau with the neural plasma membrane mediated by tau’s amino-terminal projection domain, J. Cell Biol., 131, 1327, 10.1083/jcb.131.5.1327 Brion, 1985, Neurofibrillary tangles of Alzheimer’s disease: an immunohistochemical study, J. Submicrosc. Cytol., 17, 89 Brion, 1991, A68 proteins in Alzheimer’s disease are composed of several tau isoforms in a phosphorylated state which affects their electrophoretic mobilities, Biochem. J., 279, 831, 10.1042/bj2790831 Brion, 1999, Transgenic expression of the shortest human tau affects its compartmentalization and its phosphorylation as in the pretangle stage of Alzheimer’s disease, Am. J. Pathol., 154, 255, 10.1016/S0002-9440(10)65272-8 Brion, 1991, Pick’s disease. Anatomo-clinical point of view, Rev. Neurol., 147, 693 Brown, 1992, Pick’s disease, Baillières Clin. Neurol., 1, 535 Brun, 1994, Clinical and neuropathological criteria for frontotemporal dementia, J. Neurol. Neurosurg. Psychiatry, 57, 416, 10.1136/jnnp.57.4.416 Buée, 1996, Tau proteins phosphorylation and proteolysis in a canine model of cerebral ischemia/reperfusion, Soc. Neurosci. Abstr., 22, 1897 Buée, 1999, Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick’s disease, Brain Pathol., 9, 681, 10.1111/j.1750-3639.1999.tb00550.x Buée, 1993, Binding of vascular heparan sulfate proteoglycan to Alzheimer’s amyloid precursor protein is mediated in part by the N-terminal region of A4 peptide, Brain Res., 627, 199, 10.1016/0006-8993(93)90321-D Buée, 1993, Binding of secreted human neuroblastoma proteoglycans to the Alzheimer’s amyloid A4 peptide, Brain Res., 601, 154, 10.1016/0006-8993(93)91706-X Buée, 1993, Alzheimer’s disease: Binding of vascular and neuroblastoma proteoglycans to amyloid β protein A4, Vol. 87, 217 Buée, 1996, Apolipoprotein E in Guamanian amyotrophic lateral sclerosis/parkinsonism–dementia complex: genotype analysis and relationships to neuropathological changes, Acta Neuropathol., 91, 247, 10.1007/s004010050422 Buée-Scherrer, 1995, Neurofibrillary degeneration in amyotrophic lateral sclerosis/parkinsonism–dementia complex of Guam. Immunochemical characterization of tau proteins, Am. J. Pathol., 146, 924 Buée-Scherrer, 1997, Pathological tau proteins in postencephalitic parkinsonism: comparison with Alzheimer’s disease and other neurodegenerative disorders, Ann. Neurol., 42, 356, 10.1002/ana.410420312 Buée-Scherrer, 1996, AD2, a phosphorylation-dependent monoclonal antibody directed against tau proteins found in Alzheimer’s disease, Mol. Brain Res., 39, 79, 10.1016/0169-328X(96)00003-4 Buée-Scherrer, 1996, Hyperphosphorylated tau proteins differentiate corticobasal degeneration and Pick’s disease, Acta Neuropathol., 91, 351, 10.1007/s004010050436 Bugiani, 1999, Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau, J. Neuropathol. Exp. Neurol., 58, 667, 10.1097/00005072-199906000-00011 Bussière, 1999, Phosphorylated serine422 on tau proteins is a pathological epitope found in several diseases with neurofibrillary degeneration, Acta Neuropathol., 97, 221, 10.1007/s004010050978 Butner, 1991, Tau protein binds to microtubules through a flexible array of distributed weak sites, J. Cell Biol., 115, 717, 10.1083/jcb.115.3.717 Buxton, 1992, Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy, Nature, 355, 547, 10.1038/355547a0 Caillet-Boudin, 1996, Induction of a specific tau Alzheimer epitope in SY-5Y neuroblastoma cells, NeuroReport, 8, 307, 10.1097/00001756-199612200-00061 Cambiazo, 1995, DMAP-85: a tau-like protein from Drosophila melanogaster larvae, J. Neurochem., 64, 1288, 10.1046/j.1471-4159.1995.64031288.x Carlier, 1984, Interaction between microtubule-associated protein tau and spectrin, Biochimie, 66, 305, 10.1016/0300-9084(84)90007-5 Carstea, 1997, Niemann–Pick C1 disease gene: homology to mediators of cholesterol homeostasis, Science, 277, 228, 10.1126/science.277.5323.228 Chen, 1992, Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons, Nature, 360, 674, 10.1038/360674a0 Chen, 1999, Tissue transglutaminase: an enzyme with a split personality, Int. J. Biochem. Cell. Biol., 31, 817, 10.1016/S1357-2725(99)00045-X Chen, 1986, Parkinsonism–dementia: extrapyramidal disorders, Vol. 49, 167 Chin, 1996, Glial inclusions in CNS degenerative diseases, J. Neuropathol. Exp. Neurol., 55, 499, 10.1097/00005072-199605000-00001 Chou, 1995, c-Myc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas, J. Biol. Chem., 270, 18961, 10.1074/jbc.270.32.18961 Clark, 1998, Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17, Proc. Natl. Acad. Sci. USA, 95, 13103, 10.1073/pnas.95.22.13103 Cleveland, 1977, Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly, J. Mol. Biol., 116, 227, 10.1016/0022-2836(77)90214-5 Cleveland, 1977, Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin, J. Mol. Biol., 116, 207, 10.1016/0022-2836(77)90213-3 Cohen, 1989, Protein phosphatases come of age, J. Biol. Chem., 264, 21435, 10.1016/S0021-9258(20)88197-6 Conrad, 1997, Genetic evidence for the involvement of tau in progressive supranuclear palsy, Ann. Neurol., 41, 277, 10.1002/ana.410410222 Constantinidis, 1974, Pick’s disease. Histological and clinical correlations, Eur. Neurol., 11, 208, 10.1159/000114320 Correas, 1990, The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding, Biochem. J., 269, 61, 10.1042/bj2690061 Corsellis, 1973, The aftermath of boxing, Psychol. Med., 3, 270, 10.1017/S0033291700049588 Cummings, 1984, Subcortical dementia. Review of an emerging concept, Arch. Neurol., 41, 874, 10.1001/archneur.1984.04050190080019 D’Souza, 1999, Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements, Proc. Natl. Acad. Sci. USA, 96, 5598, 10.1073/pnas.96.10.5598 Davis, 1997, Expansion of a CUG trinucleotide repeat in the 3′ untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts, Proc. Natl. Acad. Sci. USA, 94, 7388, 10.1073/pnas.94.14.7388 de Yebenes, 1995, Familial progressive supranuclear palsy. Description of a pedigree and review of the literature, Brain, 118, 1095, 10.1093/brain/118.5.1095 Delacourte, 1997, Normal and pathological Tau proteins as factors for microtubule assembly, Int. Rev. Cytol., 171, 167, 10.1016/S0074-7696(08)62588-7 Delacourte, 1999, The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease, Neurology, 52, 1158, 10.1212/WNL.52.6.1158 Delacourte, 1986, Alzheimer’s disease: Tau proteins, the promoting factors of microtubule assembly, are major components of paired helical filaments, J. Neurol. Sci., 76, 173, 10.1016/0022-510X(86)90167-X Delacourte, 1990, Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer’s disease. Demonstration with a panel of antibodies against Tau proteins, Acta Neuropathol., 80, 111, 10.1007/BF00308912 Delacourte, 1996, Specific pathological Tau protein variants characterize Pick’s disease, J. Neuropathol. Exp. Neurol., 55, 159, 10.1097/00005072-199602000-00004 Delacourte, 1998, Vulnerable neuronal subsets in Alzheimer’s and Pick’s disease are distinguished by their tau isoform distribution and phosphorylation, Ann. Neurol., 43, 193, 10.1002/ana.410430209 Delaère, 1991, Subtypes and differential laminar distributions of beta A4 deposits in Alzheimer’s disease: relationship with the intellectual status of 26 cases, Acta Neuropathol., 81, 328, 10.1007/BF00305876 Delisle, 1999, A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy, Acta Neuropathol., 98, 62, 10.1007/s004010051052 Dewar, 1995, Tau protein is altered by focal cerebral ischaemia in the rat: an immunohistochemical and immunoblotting study, Brain Res., 684, 70, 10.1016/0006-8993(95)00417-O Dewar, 1994, Cerebral ischemia induces alterations in tau and ubiquitin proteins, Dementia, 5, 168 E. Di Maria, M. Tabaton, T. Vigo, G. Abbruzzese, E. Bellone, C. Donati, E. Frasson, R. Marchese, P. Montagna, D. Munoz, P. Pramstaller, G. Zanusso, F. Ajmar, P. Mandich, Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy, Ann. Neurol. 47 (2000), in press. Ding, 1996, High molecular weight microtubule-associated proteins contain O-linked- N-acetylglucosamine, J. Biol. Chem., 271, 12555, 10.1074/jbc.271.21.12555 Dong, 1993, Glycosylation of mammalian neurofilaments. Localization of multiple O- linked N-acetylglucosamine moieties on neurofilament polypeptides L and M, J. Biol. Chem., 268, 16679, 10.1016/S0021-9258(19)85471-6 Dotti, 1987, 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, 23, 121, 10.1016/0306-4522(87)90276-4 Drechsel, 1992, Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau, Mol. Biol. Cell, 3, 1141, 10.1091/mbc.3.10.1141 Drewes, 1997, MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption, Cell, 89, 297, 10.1016/S0092-8674(00)80208-1 Drewes, 1992, Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state, EMBO J., 11, 2131, 10.1002/j.1460-2075.1992.tb05272.x Drubin, 1986, Tau protein function in living cells, J. Cell Biol., 103, 2739, 10.1083/jcb.103.6.2739 Dudek, 1993, Transglutaminase catalyzes the formation of sodium dodecyl sulfate-insoluble, Alz-50-reactive polymers of tau, J. Neurochem., 61, 1159, 10.1111/j.1471-4159.1993.tb03636.x Dudek, 1995, Postnatal changes in serine/threonine protein phosphatases and their association with the microtubules, Dev. Brain Res., 90, 54, 10.1016/0165-3806(96)83486-9 Dumanchin, 1998, Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism, Hum. Mol. Genet., 7, 1825, 10.1093/hmg/7.11.1825 Duyckaerts, 1997, Modeling the relation between neurofibrillary tangles and intellectual status, Neurobiol. Aging, 18, 267, 10.1016/S0197-4580(97)80306-5 Duyckaerts, 1986, Laminar distribution of neocortical senile plaques in senile dementia of the Alzheimer type, Acta Neuropathol., 70, 249, 10.1007/BF00686079 Ebneth, 1998, Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease, J. Cell. Biol., 777, 10.1083/jcb.143.3.777 Ezquerra, 1999, Identification of a novel polymorphism in the promoter region of the tau gene highly associated to progressive supranuclear palsy in humans, Neurosci. Lett., 275, 183, 10.1016/S0304-3940(99)00738-7 Fasulo, 1998, Tau truncation in Alzheimer’s disease: expression of a fragment encompassing PHF core tau induces apoptosis in COS cells, Alzheimer’s Rep., 1, 25 Feany, 1995, Widespread cytoskeletal pathology characterizes corticobasal degeneration, Am. J. Pathol., 146, 1388 Feany, 1995, Epitope expression and hyperphosphorylation of tau protein in corticobasal degeneration: differentiation from progressive supranuclear palsy, Acta Neuropathol., 90, 37, 10.1007/BF00294457 Feany, 1996, Neuropathologic overlap of progressive supranuclear palsy, Pick’s disease and corticobasal degeneration, J. Neuropathol. Exp. Neurol., 55, 53, 10.1097/00005072-199601000-00006 Ferreira, 1989, Microtubule formation and neurite growth in cerebellar macroneurons which develop in vitro: evidence for the involvement of the microtubule-associated proteins, MAP1a, HMW-MAP2 and Tau, Dev. Brain Res., 49, 215, 10.1016/0165-3806(89)90023-0 Flament, 1990, Correlation between microscopical changes and Tau 64 and 69 biochemical detection in senile dementia of the Alzheimer type. Tau 64 and 69 are reliable markers of the neurofibrillary degeneration, Acta Neuropathol., 80, 212, 10.1007/BF00308927 Flament, 1989, Direct demonstration of abnormal phosphorylation of Tau microtubular proteins in Alzheimer’s disease, C.R. Acad. Sci. III, 308, 77 Flament, 1990, Phosphorylation of Tau proteins: a major event during the process of neurofibrillary degeneration. A comparative study between Alzheimer’s disease and Down’s syndrome, Brain Res., 516, 15, 10.1016/0006-8993(90)90891-E Flament, 1991, Abnormal Tau proteins in progressive supranuclear palsy. Similarities and differences with the neurofibrillary degeneration of the Alzheimer type, Acta Neuropathol., 81, 591, 10.1007/BF00296367 Fleming, 1995, Modulation of the phosphorylation state of tau in situ: the roles of calcium and cyclic AMP, Biochem. J., 309, 41, 10.1042/bj3090041 Forno, 1996, Neuropathology of Parkinson’s disease, J. Neuropathol. Exp. Neurol., 55, 259, 10.1097/00005072-199603000-00001 Foster, 1997, Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference, Ann. Neurol., 41, 706, 10.1002/ana.410410606 Galasko, 1997, Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer’s disease, Neurology, 48, 632, 10.1212/WNL.48.3.632 Gao, 2000, Complex regulation of tau exon 10, whose missplicing causes frontotemporal dementia, J. Neurochem., 74, 490, 10.1046/j.1471-4159.2000.740490.x Garruto, 1991, Pacific paradigms of environmentally-induced neurological disorders: clinical, epidemiological and molecular perspectives, Neurotoxicology, 12, 347 Garver, 1994, Tau phosphorylation in human, primate, and rat brain: evidence that a pool of tau is highly phosphorylated in vivo and is rapidly dephosphorylated in vitro, J. Neurochem., 63, 2279, 10.1046/j.1471-4159.1994.63062279.x Geddes, 1993, Pathological overlap in cases of parkinsonism associated with neurofibrillary tangles. A study of recent cases of postencephalitic parkinsonism and comparison with progressive supranuclear palsy and Guamanian parkinsonism–dementia complex, Brain, 116, 281, 10.1093/brain/116.1.281 Georgieff, 1993, Expression of high molecular weight tau in the central and peripheral nervous systems, J. Cell Sci., 105, 729, 10.1242/jcs.105.3.729 Gerstmann, 1936, Über eine eigernartige hereditär-familiare Erkrankung des Zentralnervensystems, Z. Neurol., 154, 736 Ghetti, 1995, Gerstmann–Sträussler–Scheinker disease and the Indiana kindred, Brain Pathol., 5, 61, 10.1111/j.1750-3639.1995.tb00578.x Ghetti, 1996, Prion protein amyloidosis, Brain Pathol., 6, 127, 10.1111/j.1750-3639.1996.tb00796.x Giannakopoulos, 1995, Dementia lacking distinctive histopathology: Clinicopathological evaluation of 32 cases, Acta Neuropathol., 89, 346, 10.1007/BF00309628 Giannakopoulos, 1997, Cerebral cortex pathology in aging and Alzheimer’s disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts, Brain Res. Rev., 25, 217, 10.1016/S0165-0173(97)00023-4 Ginsberg, 1997, Sequestration of RNA in Alzheimer’s disease neurofibrillary tangles and senile plaques, Ann. Neurol., 41, 200, 10.1002/ana.410410211 Goedert, 1996, PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans, J. Cell Sci., 109, 2661, 10.1242/jcs.109.11.2661 Goedert, 1997, Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases, FEBS Lett., 409, 57, 10.1016/S0014-5793(97)00483-3 Goedert, 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, 10.1002/j.1460-2075.1990.tb07870.x Goedert, 1999, Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments, FEBS Lett., 450, 306, 10.1016/S0014-5793(99)00508-6 Goedert, 1994, Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer’s disease: identification of phosphorylation sites in tau protein, Biochem. J., 301, 871, 10.1042/bj3010871 Goedert, 1995, Protein phosphatase 2A is the major enzyme in brain that dephosphorylates tau protein phosphorylated by proline-directed protein kinases or cyclic AMP-dependent protein kinase, J. Neurochem., 65, 2804, 10.1046/j.1471-4159.1995.65062804.x Goedert, 1996, Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans, Nature, 383, 550, 10.1038/383550a0 Goedert, 1995, Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205, Neurosci. Lett., 189, 167, 10.1016/0304-3940(95)11484-E Goedert, 1992, Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms, Neuron, 8, 159, 10.1016/0896-6273(92)90117-V Goedert, 1999, Tau gene mutation in familial progressive subcortical gliosis, Nature Med., 5, 454, 10.1038/7454 Goedert, 1989, Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease, Neuron, 3, 519, 10.1016/0896-6273(89)90210-9 Goedert, 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, 10.1002/j.1460-2075.1989.tb03390.x Gong, 1995, Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain, J. Neurochem., 65, 732, 10.1046/j.1471-4159.1995.65020732.x Goode, 1997, Functional interactions between the proline-rich and repeat regions of tau enhance microtubule binding and assembly, Mol. Biol. Cell, 8, 353, 10.1091/mbc.8.2.353 Goode, 1994, Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau, J. Cell Biol., 124, 769, 10.1083/jcb.124.5.769 Goto, 1985, Dephosphorylation of microtubule-associated protein 2, tau factor, and tubulin by calcineurin, J. Neurochem., 45, 276, 10.1111/j.1471-4159.1985.tb05504.x Götz, 1995, Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform, EMBO J., 14, 1304, 10.1002/j.1460-2075.1995.tb07116.x Goux, 1995, Analysis of the core components of Alzheimer paired helical filaments. A gas chromatography/mass spectrometry characterization of fatty acids, carbohydrates and long-chain bases, FEBS Lett., 366, 81, 10.1016/0014-5793(95)00486-S Goux, 1996, Characterization of the glycolipid associated with Alzheimer paired helical filaments, J. Neurochem., 67, 723, 10.1046/j.1471-4159.1996.67020723.x Green, 1999, Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer’s disease, Neurosci. Lett., 259, 133, 10.1016/S0304-3940(98)00904-5 Greenberg, 1992, Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau, J. Biol. Chem., 267, 564, 10.1016/S0021-9258(18)48531-6 Greenwood, 1995, Localization and in situ phosphorylation state of nuclear tau, Exp. Cell Res., 220, 332, 10.1006/excr.1995.1323 Greenwood, 1994, Casein kinase II preferentially phosphorylates human tau isoforms containing an amino-terminal insert. Identification of threonine 39 as the primary phosphate acceptor, J. Biol. Chem., 269, 4373, 10.1016/S0021-9258(17)41790-X Griffith, 1982, The interaction of actin filaments with microtubules and microtubule-associated proteins, J. Biol. Chem., 257, 9143, 10.1016/S0021-9258(18)34254-6 Griffith, 1995, O-linked N-acetylglucosamine is upregulated in Alzheimer brains, Biochem. Biophys. Res. Commun., 213, 424, 10.1006/bbrc.1995.2149 Grover, 1999, 5′ splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10, J. Biol. Chem., 274, 15134, 10.1074/jbc.274.21.15134 Grundke-Iqbal, 1986, Microtubule-associated protein tau. A component of Alzheimer paired helical filaments, J. Biol. Chem., 261, 6084, 10.1016/S0021-9258(17)38495-8 Grundke-Iqbal, 1986, Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology, Proc. Natl. Acad. Sci. USA, 83, 4913, 10.1073/pnas.83.13.4913 Gu, 1996, Tau is widely expressed in rat tissues, J. Neurochem., 67, 1235, 10.1046/j.1471-4159.1996.67031235.x Gustafson, 1993, Clinical picture of frontal lobe degeneration of non-Alzheimer type, Dementia, 4, 143 Gustke, 1994, Domains of tau protein and interactions with microtubules, Biochemistry, 33, 9511, 10.1021/bi00198a017 Haltiwanger, 1997, O-glycosylation of nuclear and cytoplasmic proteins: regulation analogous to phosphorylation?, Biochem. Biophys. Res. Commun., 231, 237, 10.1006/bbrc.1997.6110 Haltiwanger, 1992, Glycosylation of nuclear and cytoplasmic proteins is ubiquitous and dynamic, Biochem. Soc. Trans., 20, 264, 10.1042/bst0200264 Hamre, 1989, Alz-50 immunoreactivity in the neonatal rat: changes in development and co-distribution with MAP-2 immunoreactivity, Neurosci. Lett., 98, 264, 10.1016/0304-3940(89)90411-4 Hamshere, 1997, Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes, Proc. Natl. Acad. Sci. USA, 94, 7394, 10.1073/pnas.94.14.7394 Hanger, 1991, Tau in Alzheimer’s disease and Down’s syndrome is insoluble and abnormally phosphorylated, Biochem. J., 275, 99, 10.1042/bj2750099 Hanger, 1992, Glycogen synthase kinase-3 induces Alzheimer’s disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase, Neurosci. Lett., 147, 58, 10.1016/0304-3940(92)90774-2 Harada, 1994, Altered microtubule organization in small-calibre axons of mice lacking tau protein, Nature, 369, 488, 10.1038/369488a0 Hardy, 1992, Alzheimer’s disease: the amyloid cascade hypothesis, Science, 256, 184, 10.1126/science.1566067 Harper, 1989 Hart, 1996, O-GlcNAcylation of key nuclear and cytoskeletal proteins: reciprocity with O-phosphorylation and putative roles in protein multimerization, Glycobiology, 6, 711, 10.1093/glycob/6.7.711 Hasegawa, 1996, Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein, FEBS Lett., 384, 25, 10.1016/0014-5793(96)00271-2 Hasegawa, 1992, Protein sequence and mass spectrometric analyses of tau in the Alzheimer’s disease brain, J. Biol. Chem., 267, 17047, 10.1016/S0021-9258(18)41890-X Hasegawa, 1998, Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly, FEBS Lett., 437, 207, 10.1016/S0014-5793(98)01217-4 Hasegawa, 1999, FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10, FEBS Lett., 443, 93, 10.1016/S0014-5793(98)01696-2 Hauw, 1990, Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy. Basic differences with Alzheimer’s disease and aging, Neurosci. Lett., 119, 182, 10.1016/0304-3940(90)90829-X Henriquez, 1995, Subpopulations of tau interact with microtubules and actin filaments in various cell types, Cell Biochem. Funct., 13, 239, 10.1002/cbf.290130404 Hershko, 1998, The ubiquitin system, Annu. Rev. Biochem., 67, 425, 10.1146/annurev.biochem.67.1.425 Heutink, 1997, Hereditary frontotemporal dementia is linked to chromosome 17q21-q22: a genetic and clinicopathological study of three Dutch families, Ann. Neurol., 41, 150, 10.1002/ana.410410205 Higgins, 1999, A lack of the R406W tau mutation in progressive supranuclear palsy and corticobasal degeneration, Neurology, 52, 404, 10.1212/WNL.52.2.404 Higgins, 1998, Progressive supranuclear gaze palsy is in linkage disequilibrium with the tau and not the alpha-synuclein gene, Neurology, 50, 270, 10.1212/WNL.50.1.270 Himmler, 1989, Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family, Mol. Cell. Biol., 9, 1389, 10.1128/MCB.9.4.1389 Himmler, 1989, Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains, Mol. Cell. Biol., 9, 1381, 10.1128/MCB.9.4.1381 Hirano, 1968, The fine structure of some intraganglionic alterations. Neurofibrillary tangles, granulovacuolar bodies and ‘rod-like’ structures as seen in Guam amyotrophic lateral sclerosis and parkinsonism–dementia complex, J. Neuropathol. Exp. Neurol., 27, 167, 10.1097/00005072-196804000-00001 Hirano, 1961, Parkinsonism–dementia complex, an endemic disease on the island of Guam I. Clinical features, Brain, 84, 642, 10.1093/brain/84.4.642 Hirano, 1966, Amyotrophic lateral sclerosis and Parkinsonism–dementia complex on Guam. Further pathologic studies, Arch. Neurol., 15, 35, 10.1001/archneur.1966.00470130039004 Hirokawa, 1996, 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, J. Cell Biol., 132, 667, 10.1083/jcb.132.4.667 Hirokawa, 1988, Tau proteins: the molecular structure and mode of binding on microtubules, J. Cell Biol., 107, 1449, 10.1083/jcb.107.4.1449 Hock, 1998, Histological markers in nasal mucosa of patients with Alzheimer’s disease, Eur. Neurol., 40, 31, 10.1159/000007953 Hock, 1995, Increased levels of tau protein in cerebrospinal fluid of patients with Alzheimer’s disease-correlation with degree of cognitive impairment, Ann. Neurol., 37, 414, 10.1002/ana.410370325 Hof, 1992, Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer’s disease cases, Acta Neuropathol., 85, 23, 10.1007/BF00304630 Hof, 1999, Cortical neuropathology in aging and dementing disorders: neuronal typology, connectivity, and selective vulnerability, Vol. 14, 175 Hof, 1994, Quantitative neuropathologic analysis of Pick’s disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer’s disease, Acta Neuropathol., 87, 115, 10.1007/BF00296179 Hof, 1995, Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down’s syndrome. Quantitative regional analysis and comparison with Alzheimer’s disease, Arch. Neurol., 52, 379, 10.1001/archneur.1995.00540280065020 Hof, 1992, Distribution of neurofibrillary tangles and senile plaques in the cerebral cortex in postencephalitic parkinsonism, Neurosci. Lett., 139, 10, 10.1016/0304-3940(92)90846-Y Hof, 1990, Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer’s disease: I. Superior frontal and inferior temporal cortex, J. Comp. Neurol., 301, 44, 10.1002/cne.903010105 Hof, 1992, Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases, Acta Neuropathol., 84, 45, 10.1007/BF00427214 P.R. Hof, J.H. Morrison, The cellular basis of cortical disconnection in Alzheimer disease and related dementing conditions, in: R.D. Terry, R. Katzman, K.L. Bick, S.S. Sisodia (Eds.), Alzheimer Disease, Lippincott Williams and Wilkins, Philadelphia, 1999, 207–232. Hof, 1994, Amyotrophic lateral sclerosis/parkinsonism–dementia complex of Guam: quantitative neuropathology, immunohistochemical analysis of neuronal vulnerability, and comparison with related neurodegenerative disorders, Acta Neuropathol., 88, 397, 10.1007/BF00389490 Hof, 1995, Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices, J. Comp. Neurol., 362, 109, 10.1002/cne.903620107 Hof, 1991, Neurofibrillary tangle distribution in the cerebral cortex of parkinsonism–dementia cases from Guam: differences with Alzheimer’s disease, Brain Res., 564, 306, 10.1016/0006-8993(91)91467-F Hoffmann, 1997, Unique Alzheimer’s disease paired helical filament specific epitopes involve double phosphorylation at specific sites, Biochemistry, 36, 8114, 10.1021/bi970380+ Holt, 1987, Erythrocytes contain cytoplasmic glycoproteins. O-linked GlcNAc on Band 4.1, J. Biol. Chem., 262, 14847, 10.1016/S0021-9258(18)48100-8 Holzer, 1994, Abnormally phosphorylated tau protein in Alzheimer’s disease: heterogeneity of individual regional distribution and relationship to clinical severity, Neuroscience, 63, 499, 10.1016/0306-4522(94)90546-0 Hong, 1998, Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17, Science, 282, 1914, 10.1126/science.282.5395.1914 Hulstaert, 1999, Improved discrimination of AD patients using beta-amyloid(1–42) and tau levels in CSF, Neurology, 52, 1555, 10.1212/WNL.52.8.1555 Hutton, 1998, Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17, Nature, 393, 702, 10.1038/31508 Hwang, 1996, Activation of phospholipase C-gamma by the concerted action of tau proteins and arachidonic acid, J. Biol. Chem., 271, 18342, 10.1074/jbc.271.31.18342 Hyman, 1997, Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease, J. Neuropathol. Exp. Neurol., 56, 1095, 10.1097/00005072-199710000-00002 Ihara, 1986, Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer’s disease, J. Biochem., 99, 1807, 10.1093/oxfordjournals.jbchem.a135662 Iijima, 1999, A distinct familial presenile dementia with a novel missense mutation in the tau gene, NeuroReport, 10, 497, 10.1097/00001756-199902250-00010 Ingebritsen, 1983, Protein phosphatases: properties and role in cellular regulation, Science, 221, 331, 10.1126/science.6306765 Ingelson, 1996, Microtubule-associated protein tau in human fibroblasts with the Swedish Alzheimer mutation, Neurosci. Lett., 220, 9, 10.1016/S0304-3940(96)13218-3 Irminger-Finger, 1990, Analysis of the primary sequence and microtubule-binding region of the Drosophila 205K MAP, J. Cell Biol., 111, 2563, 10.1083/jcb.111.6.2563 Ishihara, 1999, Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform, Neuron, 24, 751, 10.1016/S0896-6273(00)81127-7 Ishino, 1976, Frequency of Alzheimer’s neurofibrillary tangles in the cerebral cortex in progressive supranuclear palsy (subcortical argyrophilic dystrophy), J. Neurol. Sci., 28, 309, 10.1016/0022-510X(76)90024-1 Isoe, 1996, Tau proteins in cerebrospinal fluid from patients with Alzheimer’s disease: a longitudinal study, Dementia, 7, 175 Jaspert, 1995, Myotonic dystrophy: correlation of clinical symptoms with the size of the CTG trinucleotide repeat, J. Neurol., 242, 99, 10.1007/BF00887824 Jenkins, 1998, Tau complexes with phospholipase C-gamma in situ, NeuroReport, 9, 67, 10.1097/00001756-199801050-00014 Jenkins, 2000, Modulation of tau phosphorylation and intracellular localization by cellular stress, Biochem. J., 345, 263, 10.1042/0264-6021:3450263 Jensen, 1995, Increased cerebrospinal fluid tau in patients with Alzheimer’s disease, Neurosci. Lett., 186, 189, 10.1016/0304-3940(95)11297-A Jicha, 1997, A conformation- and phosphorylation-dependent antibody recognizing the paired helical filaments of Alzheimer’s disease, J. Neurochem., 69, 2087, 10.1046/j.1471-4159.1997.69052087.x Jicha, 1999, Hierarchical phosphorylation of recombinant tau by the paired-helical filament-associated protein kinase is dependent on cyclic AMP-dependent protein kinase, J. Neurochem., 72, 214, 10.1046/j.1471-4159.1999.0720214.x Johnson, 1992, Differential phosphorylation of tau by cyclic AMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase II: metabolic and functional consequences, J. Neurochem., 59, 2056, 10.1111/j.1471-4159.1992.tb10094.x Johnson, 1997, The tau protein in human cerebrospinal fluid in Alzheimer’s disease consists of proteolytically derived fragments, J. Neurochem., 68, 430, 10.1046/j.1471-4159.1997.68010430.x Kampers, 1996, RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments, FEBS Lett., 399, 344, 10.1016/S0014-5793(96)01386-5 Kanai, 1998, Longitudinal study of cerebrospinal fluid levels of tau, Abeta 1–40, and Abeta 1–42(43) in Alzheimer’s disease: a study in Japan, Ann. Neurol., 44, 17, 10.1002/ana.410440108 Kent, 1985, Evidence for glucose-mediated covalent cross-linking of collagen after glycosylation in vitro, Biochem. J., 225, 745, 10.1042/bj2250745 Kidd, 1963, Paired helical filaments in electron microscopy of Alzheimer’s disease, Nature, 197, 192, 10.1038/197192b0 Kiuchi, 1991, Presenile appearance of abundant Alzheimer’s neurofibrillary tangles without senile plaques in the brain in myotonic dystrophy, Acta Neuropathol., 82, 1, 10.1007/BF00310916 Ko, 1999, An immunochemical study on tau glycation in paired helical filaments, Brain Res., 830, 301, 10.1016/S0006-8993(99)01415-8 Kondratick, 1996, Alzheimer’s disease neurofibrillary tangles contain mitosis-specific phosphoepitopes, J. Neurochem., 67, 2405, 10.1046/j.1471-4159.1996.67062405.x Korneyev, 1995, Rapid reversible phosphorylation of rat brain tau proteins in response to cold water stress, Neurosci. Lett., 191, 19, 10.1016/0304-3940(95)11546-3 Kosik, 1987, MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: an immunocytochemical study of cultured rat cerebrum, J. Neurosci., 7, 3142, 10.1523/JNEUROSCI.07-10-03142.1987 Kosik, 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, 10.1073/pnas.83.11.4044 Kosik, 1989, Along the way to a neurofibrillary tangle: a look at the structure of tau, Ann. Med., 21, 109, 10.3109/07853898909149195 Kosik, 1989, Developmentally regulated expression of specific tau sequences, Neuron, 2, 1389, 10.1016/0896-6273(89)90077-9 Kovacs, 1999, beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer’s disease, Neuropathol. Appl. Neurobiol., 25, 481, 10.1046/j.1365-2990.1999.00208.x Kreppel, 1997, Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats, J. Biol. Chem., 272, 9308, 10.1074/jbc.272.14.9308 Ksiezak-Reding, 1992, Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments, Brain Res., 597, 209, 10.1016/0006-8993(92)91476-U Ksiezak-Reding, 1994, Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration, Am. J. Pathol., 145, 1496 Kumagae, 1999, Human c-Jun N-terminal kinase expression and activation in the nervous system, Mol. Brain Res., 67, 10, 10.1016/S0169-328X(99)00013-3 Kurz, 1998, Tau protein in cerebrospinal fluid is significantly increased at the earliest clinical stage of Alzheimer disease, Alzheimer Dis. Assoc. Disord., 12, 372, 10.1097/00002093-199812000-00020 Ladner, 1996, Reduction of calcineurin enzymatic activity in Alzheimer’s disease: correlation with neuropathologic changes, J. Neuropathol. Exp. Neurol., 55, 924, 10.1097/00005072-199608000-00008 Ledesma, 1995, Tau protein from Alzheimer’s disease patients is glycated at its tubulin-binding domain, J. Neurochem., 65, 1658, 10.1046/j.1471-4159.1995.65041658.x Lee, 1988, The primary structure and heterogeneity of tau protein from mouse brain, Science, 239, 285, 10.1126/science.3122323 Lee, 1996, A new molecular interactor for tau protein, Soc. Neurosci. Abstr., 22, 975 Lee, 1989, The microtubule binding domain of tau protein, Neuron, 2, 1615, 10.1016/0896-6273(89)90050-0 Lee, 1998, Tau interacts with src-family non-receptor tyrosine kinases, J. Cell Sci., 111, 3167, 10.1242/jcs.111.21.3167 Lee, 1992, Expression of tau protein in non-neuronal cells: microtubule binding and stabilization, J. Cell Sci., 102, 227, 10.1242/jcs.102.2.227 Lee, 1993, Tau proteins are abnormally expressed in olfactory epithelium of Alzheimer patients and developmentally regulated in human fetal spinal cord, Exp. Neurol., 121, 93, 10.1006/exnr.1993.1074 Lee, 1991, A68: a major subunit of paired helical filaments and derivatized forms of normal Tau, Science, 251, 675, 10.1126/science.1899488 Lefebvre, 1999, Effect of okadaic acid on O-linked N-acetylglucosamine levels in a neuroblastoma cell line, Biochim Biophys Acta, 1472, 71, 10.1016/S0304-4165(99)00105-1 Leterrier, 1982, Interactions between neurofilaments and microtubule-associated proteins: a possible mechanism for intraorganellar bridging, J. Cell Biol., 95, 982, 10.1083/jcb.95.3.982 Liao, 1998, Protein phosphatase 1 is targeted to microtubules by the microtubule-associated protein Tau, J. Biol. Chem., 273, 21901, 10.1074/jbc.273.34.21901 Lindwall, 1984, Phosphorylation affects the ability of tau protein to promote microtubule assembly, J. Biol. Chem., 259, 5301, 10.1016/S0021-9258(17)42989-9 Litersky, 1992, Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain, J. Biol. Chem., 267, 1563, 10.1016/S0021-9258(18)45982-0 Litvan, 1997, The clinical and pathologic hallmarks of progressive supranuclear palsy, Curr. Opin. Neurol., 10, 346, 10.1097/00019052-199708000-00011 Litvan, 1996, Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome), Neurology, 46, 922, 10.1212/WNL.46.4.922 Litvan, 1996, Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders, J. Neuropathol. Exp. Neurol., 55, 97, 10.1097/00005072-199601000-00010 Liu, 1995, Detection of a Cdc2-related kinase associated with Alzheimer paired helical filaments, Am. J. Pathol., 146, 228 Liu, 1997, Tau-like proteins in the nervous system of goldfish, Neurochem. Res., 22, 1511, 10.1023/A:1021914830872 Loftus, 1997, Murine model of Niemann–Pick C disease: mutation in a cholesterol homeostasis gene, Science, 277, 232, 10.1126/science.277.5323.232 Love, 1995, Neurofibrillary tangles in Niemann–Pick disease type C, Brain, 118, 119, 10.1093/brain/118.1.119 Lovestone, 1997, The phosphorylation of tau: a critical stage in neurodevelopment and neurodegenerative processes, Neuroscience, 78, 309 Lynch, 1994, Clinical characteristics of a family with chromosome 17-linked disinhibition–dementia–parkinsonism–amyotrophy complex, Neurology, 44, 1878, 10.1212/WNL.44.10.1878 Mailliot, 1998, Alzheimer-specific epitope of AT100 in transfected cell lines with tau: toward an efficient cell model of tau abnormal phosphorylation, Neurosci. Lett., 255, 13, 10.1016/S0304-3940(98)00693-4 C. Mailliot, V. Podevin-Dimster, R. Rosenthal, N. Sergeant, A. Delacourte, G. Fiskum, L. Buée, Rapid tau dephosphorylation and rephosphorylation during cadiac arrest-induced cerebral ischemia and reperfusion, J. Cereb. Blood Flow Metab. 2000, in press. Mailliot, 1998, Phosphorylation of specific sets of tau isoforms reflects different neurofibrillary degeneration processes, FEBS Lett., 433, 201, 10.1016/S0014-5793(98)00910-7 Malandrini, 1995, Ultrastructure and immunoreactivity of dystrophic axons indicate a different pathogenesis of Hallervorden–Spatz disease and infantile neuroaxonal dystrophy, Virchows Arch., 427, 415, 10.1007/BF00199391 Mandell, 1995, The microtubule cytoskeleton and the development of neuronal polarity, Neurobiol. Aging, 16, 229, 10.1016/0197-4580(94)00164-V Mann, 1989, An analysis of the morphology of senile plaques in Down’s syndrome patients of different ages using immunocytochemical and lectin histochemical techniques, Neuropathol. Appl. Neurobiol., 15, 317, 10.1111/j.1365-2990.1989.tb01232.x Mann, 1984, Alzheimer’s presenile dementia, senile dementia of Alzheimer type and Down’s syndrome in middle age form an age related continuum of pathological changes, Neuropathol. Appl. Neurobiol., 10, 185, 10.1111/j.1365-2990.1984.tb00351.x Matsuo, 1994, Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer’s disease paired helical filament tau, Neuron, 13, 989, 10.1016/0896-6273(94)90264-X Mattiace, 1991, A new neuritic plaque without amyloid in corticonigral degeneration with neuronal achromasia, J. Neuropathol. Exp. Neurol., 50, 310 Matus, 1994, Stiff microtubules and neuronal morphology, Trends Neurosci., 17, 19, 10.1016/0166-2236(94)90030-2 Mawal-Dewan, 1994, The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases, J. Biol. Chem., 269, 30981, 10.1016/S0021-9258(18)47378-4 McDermott, 1996, ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins, Biochemistry, 35, 9415, 10.1021/bi952646n McKhann, 1984, Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease, Neurology, 34, 939, 10.1212/WNL.34.7.939 McQuaid, 1994, Association of measles virus with neurofibrillary tangles in subacute sclerosing panencephalitis: a combined in situ hybridization and immunocytochemical investigation, Neuropathol. Appl. Neurobiol., 20, 103, 10.1111/j.1365-2990.1994.tb01168.x Miller, 1995, Transglutaminase cross-linking of the tau protein, J. Neurochem., 65, 1760, 10.1046/j.1471-4159.1995.65041760.x Miyata, 1986, Binding of microtubule-associated protein 2 and tau to the intermediate filament reassembled from neurofilament 70 kDa subunit protein. Its regulation by calmodulin, J. Biol. Chem., 261, 13026, 10.1016/S0021-9258(18)69265-8 Mohit, 1995, p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system, Neuron, 14, 67, 10.1016/0896-6273(95)90241-4 Mori, 1995, Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau, Neurosci. Lett., 186, 181, 10.1016/0304-3940(95)11291-4 Mori, 1987, Ubiquitin is a component of paired helical filaments in Alzheimer’s disease, Science, 235, 1641, 10.1126/science.3029875 Morishima-Kawashima, 1993, Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments, Neuron, 10, 1151, 10.1016/0896-6273(93)90063-W Morishima-Kawashima, 1995, Proline-directed and non-proline-directed phosphorylation of PHF-tau, J. Biol. Chem., 270, 823, 10.1074/jbc.270.2.823 Morris, 1999, The tau gene A0 polymorphism in progressive supranuclear palsy and related neurodegenerative diseases, J. Neurol. Neurosurg. Psychiatry, 66, 665, 10.1136/jnnp.66.5.665 Motter, 1995, Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease, Ann. Neurol., 38, 643, 10.1002/ana.410380413 Mulot, 1994, PHF-tau from Alzheimer’s brain comprises four species on SDS–PAGE which can be mimicked by in vitro phosphorylation of human brain tau by glycogen synthase kinase-3 beta, FEBS Lett., 349, 359, 10.1016/0014-5793(94)00702-0 Munroe, 1995, Tau protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer’s disease, Ann. Clin. Lab. Sci., 25, 207 Murrell, 1997, Familial multiple-system tauopathy with presenile dementia is localized to chromosome 17, Am. J. Hum. Genet., 61, 1131, 10.1086/301594 Murrell, 1999, Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits, J. Neuropathol. Exp. Neurol., 58, 1207, 10.1097/00005072-199912000-00002 Nacharaju, 1997, Characterization of in vitro glycation sites of tau, J. Neurochem., 69, 1709, 10.1046/j.1471-4159.1997.69041709.x Namba, 1991, Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt–Jakob disease, Brain Res., 541, 163, 10.1016/0006-8993(91)91092-F Nelson, 1996, Molecular evolution of tau protein: implications for Alzheimer’s disease, J. Neurochem., 67, 1622, 10.1046/j.1471-4159.1996.67041622.x Neve, 1986, Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2, Brain Res., 387, 271, 10.1016/0169-328X(86)90033-1 Nixon, 1991, Neurofilament phosphorylation: a new look at regulation and function, Trends Neurosci., 14, 501, 10.1016/0166-2236(91)90062-Y Norlund, 1999, Elevated transglutaminase-induced bonds in PHF tau in Alzheimer’s disease, Brain Res., 851, 154, 10.1016/S0006-8993(99)02179-4 Novak, 1994, Truncated tau protein as a new marker for Alzheimer’s disease, Acta Virol., 38, 173 Oliva, 1998, Significant changes in the tau A0 and A3 alleles in progressive supranuclear palsy and improved genotyping by silver detection, Arch. Neurol., 55, 1122, 10.1001/archneur.55.8.1122 Ono, 1987, Neuropathological changes of the brain in myotonic dystrophy-some new observations, J. Neurol. Sci., 81, 301, 10.1016/0022-510X(87)90105-5 Ono, 1995, Dephosphorylation of abnormal sites of tau factor by protein phosphatases and its implication for Alzheimer’s disease, Neurochem. Int., 26, 205, 10.1016/0197-0186(94)00135-H Oyanagi, 1994, Amyotrophic lateral sclerosis of Guam: the nature of the neuropathological findings, Acta Neuropathol., 88, 405, 10.1007/BF00389491 Oyanagi, 1994, Topographic investigation of brain atrophy in parkinsonism–dementia complex of Guam: a comparison with Alzheimer’s disease and progressive supranuclear palsy, Neurodegeneration, 3, 301 Panda, 1995, Kinetic stabilization of microtubule dynamics at steady state by tau and microtubule-binding domains of tau, Biochemistry, 34, 11117, 10.1021/bi00035a017 Papasozomenos, 1996, Heat shock induces rapid dephosphorylation of tau in both female and male rats followed by hyperphosphorylation only in female rats: implications for Alzheimer’s disease, J. Neurochem., 66, 1140, 10.1046/j.1471-4159.1996.66031140.x Papasozomenos, 1997, The heat shock-induced hyperphosphorylation of tau is estrogen-independent and prevented by androgens: implications for Alzheimer disease, Proc. Natl. Acad. Sci. USA, 94, 6612, 10.1073/pnas.94.13.6612 Pastor, 2000, Significant association between the tau gene A0/A0 genotype and Parkinson’s disease, Ann. Neurol., 47, 242, 10.1002/1531-8249(200002)47:2<242::AID-ANA16>3.0.CO;2-L Paudel, 1999, Heparin-induced conformational change in microtubule-associated protein Tau as detected by chemical cross-linking and phosphopeptide mapping, J. Biol. Chem., 274, 8029, 10.1074/jbc.274.12.8029 Paulus, 1990, Corticonigral degeneration with neuronal achromasia and basal neurofibrillary tangles, Acta Neuropathol., 81, 89, 10.1007/BF00662643 Perez, 1996, Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau–tau interaction, J. Neurochem., 67, 1183, 10.1046/j.1471-4159.1996.67031183.x Pérez-Tur, 1999, Neurodegenerative diseases of Guam: analysis of TAU, Neurology, 53, 411, 10.1212/WNL.53.2.411 Perl, 1980, Alzheimer’s disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons, Science, 208, 297, 10.1126/science.7367858 Perl, 1991, Aluminum, Alzheimer’s disease, and the olfactory system, Ann. N.Y. Acad. Sci., 640, 8, 10.1111/j.1749-6632.1991.tb00183.x S. Pickering-Brown, H. Houlden, M. Baker, J. Adamson, F. Owen, D. Neary, D. Craufurd, J. Snowden, D. Mann, M. Hutton, Pick’s Disease is associated with mutations in the tau gene, submitted Poirier, 1995, Apolipoprotein E, synaptic plasticity and Alzheimer’s disease, Ann. Med., 27, 663, 10.3109/07853899509019253 Pollock, 1986, Filamentous aggregates in Pick’s disease, progressive supranuclear palsy, and Alzheimer’s disease share antigenic determinants with microtubule-associated protein tau, Lancet, 2, 1211, 10.1016/S0140-6736(86)92212-9 Poorkaj, 1998, Tau is a candidate gene for chromosome 17 frontotemporal dementia, Ann. Neurol., 43, 815, 10.1002/ana.410430617 Pope, 1993, Phosphorylated tau epitope of Alzheimer’s disease is coupled to axon development in the avian central nervous system, Exp. Neurol., 120, 106, 10.1006/exnr.1993.1044 Probst, 1988, Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles. Very similar antigenicity of subcortical neuronal pathology in progressive supranuclear palsy and Alzheimer’s disease, Acta Neuropathol., 77, 61, 10.1007/BF00688244 Probst, 1996, Pick’s disease: hyperphosphorylated tau protein segregates to the somatoaxonal compartment, Acta Neuropathol., 92, 588, 10.1007/s004010050565 Rebeiz, 1968, Corticodentatonigral degeneration with neuronal achromasia, Arch. Neurol., 18, 20, 10.1001/archneur.1968.00470310034003 Rebhan, 1995, Complementary distribution of tau proteins in different phosphorylation states within growing axons, NeuroReport, 6, 429, 10.1097/00001756-199502000-00006 Reed, 1998, The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia (’pallido-ponto-nigral degeneration’), J. Neuropathol. Exp. Neurol., 57, 588, 10.1097/00005072-199806000-00006 Rendon, 1990, Interaction of microtubules and microtubule-associated proteins (MAPs) with rat brain mitochondria, Biochem. J., 269, 555, 10.1042/bj2690555 N.B. Rewcastle, Degenerative diseases of the central nervous system, in: R.L. Davis, D.M. Robertson (Eds.), Textbook of Neuropathology, Williams and Wilkins, Baltimore, 1991, 903–961. Reyes, 1993, Olfactory-related changes in Alzheimer’s disease: a quantitative neuropathologic study, Brain Res. Bull., 32, 1, 10.1016/0361-9230(93)90310-8 Reynolds, 1997, Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau protein, J. Neurochem., 68, 1736, 10.1046/j.1471-4159.1997.68041736.x Riederer, 1994, Differential distribution of tau proteins in developing cat cerebellum, Brain Res. Bull., 33, 155, 10.1016/0361-9230(94)90245-3 Riemenschneider, 1996, Cerebrospinal protein tau is elevated in early Alzheimer’s disease, Neurosci. Lett., 212, 209, 10.1016/0304-3940(96)12810-X Rinne, 1994, Corticobasal degeneration. A clinical study of 36 cases, Brain, 117, 1183, 10.1093/brain/117.5.1183 Rizzu, 1999, High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands, Am. J. Hum. Genet., 64, 414, 10.1086/302256 Rocca, 1991, M. K., D.W. O’Connor, A. Da Silva Droux, R. Sulkava, D.W.K. Kay, L. Amaducci, Frequency and distribution of Alzheimer’s disease in Europe: a collaborative study of 1980–1990 prevalence findings. The EURODEM- Prevalence Research Group, Ann. Neurol., 30, 381, 10.1002/ana.410300310 Roder, 1997, Phosphorylation-dependent monoclonal Tau antibodies do not reliably report phosphorylation by extracellular signal-regulated kinase 2 at specific sites, J. Biol. Chem., 272, 4509, 10.1074/jbc.272.7.4509 Rosenthal, 1992, Prevention of postischemic canine neurological injury through potentiation of brain energy metabolism by acetyl-l-carnitine, Stroke, 23, 1312, 10.1161/01.STR.23.9.1312 Rosner, 1995, Developmental expression of tau proteins in the chicken and rat brain: rapid down-regulation of a paired helical filament epitope in the rat cerebral cortex coincides with the transition from immature to adult tau isoforms, Int. J. Dev. Neurosci., 13, 607, 10.1016/0736-5748(95)00042-F Sadot, 1996, Identification of a tau promoter region mediating tissue-specific-regulated expression in PC12 cells, J. Mol. Biol., 256, 805, 10.1006/jmbi.1996.0126 Saito, 1995, In situ dephosphorylation of tau by protein phosphatase 2A and 2B in fetal rat primary cultured neurons, FEBS Lett., 376, 238, 10.1016/0014-5793(95)01292-0 Sasaki, 1998, Advanced glycation end products in Alzheimer’s disease and other neurodegenerative diseases, Am. J. Pathol., 153, 1149, 10.1016/S0002-9440(10)65659-3 Sattilaro, 1981, Microtubule-associated proteins (MAPs) and the organization of actin filaments in vitro, J. Cell Biol., 90, 467, 10.1083/jcb.90.2.467 Sawa, 1994, Molecular diversity at the carboxyl terminus of human and rat tau, Mol. Brain Res., 27, 111, 10.1016/0169-328X(94)90191-0 Schmidt, 1996, Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer’s disease PHFtau, J. Neuropathol. Exp. Neurol., 55, 534, 10.1097/00005072-199605000-00006 Schoenfeld, 1994, Diverse distribution and function of fibrous microtubule-associated proteins in the nervous system, Int. Rev. Cytol., 151, 67, 10.1016/S0074-7696(08)62631-5 Schumacher, 1998, The murine Polycomb-group gene eed and its human orthologue: functional implications of evolutionary conservation, Genomics, 54, 79, 10.1006/geno.1998.5509 Schweers, 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, 10.1073/pnas.92.18.8463 Scott, 1993, Aggregation of tau protein by aluminum, Brain Res., 628, 77, 10.1016/0006-8993(93)90940-O Selden, 1983, Phosphorylation of microtubule-associated proteins regulates their interaction with actin filaments, J. Biol. Chem., 258, 7064, 10.1016/S0021-9258(18)32333-0 Sergeant, 1995, Isoelectric point differentiates PHF-tau from biopsy-derived human brain tau proteins, NeuroReport, 6, 2217, 10.1097/00001756-199511000-00028 Sergeant, 1997, Two-dimensional characterization of paired helical filament-tau from Alzheimer’s disease: demonstration of an additional 74 kDa component and age-related biochemical modifications, J. Neurochem., 69, 834, 10.1046/j.1471-4159.1997.69020834.x Sergeant, 1997, Different distribution of phosphorylated tau protein isoforms in Alzheimer’s and Pick’s diseases, FEBS Lett., 412, 578, 10.1016/S0014-5793(97)00859-4 Sergeant, 1999, Neurofibrillary degeneration in progressive supranuclear palsy and corticobasal degeneration: tau pathologies with exclusively ‘exon 10’ isoforms, J. Neurochem., 72, 1243, 10.1046/j.1471-4159.1999.0721243.x Seubert, 1995, Detection of phosphorylated Ser262 in fetal tau, adult tau, and paired helical filament tau, J. Biol. Chem., 270, 18917, 10.1074/jbc.270.32.18917 Shackelford, 1996, Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit spinal cord, J. Neurochem., 66, 286, 10.1046/j.1471-4159.1996.66010286.x Shin, 1997, Interaction of aluminum with paired helical filament tau is involved in neurofibrillary pathology of Alzheimer’s disease, Gerontology, 43, 16, 10.1159/000213882 Simon, 1995, The extra sex combs product contains WD40 repeats and its time of action implies a role distinct from other Polycomb group products, Mech. Dev., 53, 197, 10.1016/0925-4773(95)00434-3 Singh, 1996, Non-proline-dependent protein kinases phosphorylate several sites found in tau from Alzheimer disease brain, Mol. Cell. Biochem., 154, 143, 10.1007/BF00226782 Skoog, 1995, A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele, Neurodegeneration, 4, 433, 10.1006/neur.1995.0052 Smith, 1996, Quantitative solubilization and analysis of insoluble paired helical filaments from Alzheimer disease, Brain Res., 717, 99, 10.1016/0006-8993(95)01473-X Smith, 1994, Advanced Maillard reaction end products are associated with Alzheimer disease pathology, Proc. Natl. Acad. Sci. USA, 91, 5710, 10.1073/pnas.91.12.5710 Snow, 1995, Differential binding of vascular cell-derived proteoglycans (perlecan, biglycan, decorin, and versican) to the beta-amyloid protein of Alzheimer’s disease, Arch. Biochem. Biophys., 320, 84, 10.1006/abbi.1995.1345 Snow, 1992, Peripheral distribution of dermatan sulfate proteoglycans (decorin) in amyloid-containing plaques and their presence in neurofibrillary tangles of Alzheimer’s disease, J. Histochem. Cytochem., 40, 105, 10.1177/40.1.1370306 Snow, 1987, Sulfated glycosaminoglycans in Alzheimer’s disease, Hum. Pathol., 18, 506, 10.1016/S0046-8177(87)80036-9 Song, 1997, Low initial tau phosphorylation in human brain biopsy samples, Neurobiol. Aging, 18, 475, 10.1016/S0197-4580(97)00043-2 Sontag, 1995, A novel pool of protein phosphatase 2A is associated with microtubules and is regulated during the cell cycle, J. Cell Biol., 128, 1131, 10.1083/jcb.128.6.1131 Sontag, 1999, Molecular Interactions among Protein Phosphatase 2A, Tau, and Microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies, J. Biol. Chem., 274, 25490, 10.1074/jbc.274.36.25490 Soulié, 1996, Dephosphorylation studies of SKNSH-SY 5Y cell Tau proteins by endogenous phosphatase activity, Neurosci. Lett., 206, 189, 10.1016/S0304-3940(96)12472-1 Spillantini, 1998, Frontotemporal dementia and parkinsonism linked to chromosome 17: a new group of tauopathies, Brain Pathol., 8, 387, 10.1111/j.1750-3639.1998.tb00162.x Spillantini, 1998, Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau, Am. J. Pathol., 153, 1359, 10.1016/S0002-9440(10)65721-5 Spillantini, 1998, Mutation in the tau gene in familial multiple system tauopathy with presenile dementia, Proc. Natl. Acad. Sci. USA, 95, 7737, 10.1073/pnas.95.13.7737 Spillantini, 1997, Alpha-synuclein in Lewy bodies, Nature, 388, 839, 10.1038/42166 Spillantini, 1999, Microtubule-associated protein tau, heparan sulphate and alpha-synuclein in several neurodegenerative diseases with dementia, Acta Neuropathol., 97, 585, 10.1007/s004010051034 Spittaels, 1999, Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein, Am. J. Pathol., 155, 2153, 10.1016/S0002-9440(10)65533-2 Steele, 1964, Progressive supranuclear palsy. A heterogeneous degeneration involving brain stem, basal ganglia and cerebellum with vertical gaze ans pseudobulbar palsy, nuchal dystonia and dementia, Arch. Neurol, 333, 10.1001/archneur.1964.00460160003001 Strittmatter, 1994, Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease, Proc. Natl. Acad. Sci. USA, 91, 11183, 10.1073/pnas.91.23.11183 Szendrei, 1993, Recognition of the minimal epitope of monoclonal antibody Tau-1 depends upon the presence of a phosphate group but not its location, J. Neurosci. Res., 34, 243, 10.1002/jnr.490340212 Takahashi, 1995, Involvement of tau protein kinase I in paired helical filament-like phosphorylation of the juvenile tau in rat brain, J. Neurochem., 64, 1759, 10.1046/j.1471-4159.1995.64041759.x Takashima, 1998, Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau, Proc. Natl. Acad. Sci. USA, 95, 9637, 10.1073/pnas.95.16.9637 Talamo, 1991, Pathologic changes in olfactory neurons in Alzheimer’s disease, Ann. N.Y. Acad. Sci., 640, 1, 10.1111/j.1749-6632.1991.tb00182.x Talamo, 1989, Pathological changes in olfactory neurons in patients with Alzheimer’s disease, Nature, 337, 736, 10.1038/337736a0 Tellez-Nagel, 1973, Ultrastructure of neurofibrillary tangles in Steele–Richardson–Olszewski syndrome, Arch. Neurol., 29, 324, 10.1001/archneur.1973.00490290064007 Thurston, 1996, Tau as a nucleolar protein in human nonneural cells in vitro and in vivo, Chromosoma, 105, 20, 10.1007/BF02510035 Tissot, 1985, Pick’s disease, Vol. 46, 233 Tolnay, 1999, Tau protein pathology in Alzheimer’s disease and related disorders, Neuropathol. Appl. Neurobiol, 25, 171, 10.1046/j.1365-2990.1999.00182.x Tomlinson, 1968, Observations on the brains of non-demented old people, J. Neurol. Sci., 7, 331, 10.1016/0022-510X(68)90154-8 Tomonaga, 1977, Ultrastructure of neurofibrillary tangles in progressive supranuclear palsy, Acta Neuropathol., 37, 177, 10.1007/BF00692065 Tranchant, 1997, Neurofibrillary tangles in Gerstmann–Sträussler–Scheinker syndrome with the A117V prion gene mutation, J. Neurol. Neurosurg. Psychiatry, 63, 240, 10.1136/jnnp.63.2.240 Trojanowski, 1995, Phosphorylation of paired helical filament tau in Alzheimer’s disease neurofibrillary lesions: focusing on phosphatases, FASEB J., 9, 1570, 10.1096/fasebj.9.15.8529836 Tucholski, 1999, Tau is modified by tissue transglutaminase in situ: possible functional and metabolic effects of polyamination, J. Neurochem., 73, 1871, 10.1046/j.1471-4159.1999.01871.x Tucker, 1990, The roles of microtubule-associated proteins in brain morphogenesis: a review, Brain Res. Rev., 15, 101, 10.1016/0165-0173(90)90013-E Turpin, 1991, Type C Niemann–Pick disease: supranuclear ophthalmoplegia associated with deficient biosynthesis of cholesterol esters, Rev. Neurol., 147, 28 Vandermeeren, 1993, Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay, J. Neurochem., 61, 1828, 10.1111/j.1471-4159.1993.tb09823.x Vanier, 1998, Expression of specific tau exons in normal and tumoral pancreatic acinar cells, J. Cell Sci., 111, 1419, 10.1242/jcs.111.10.1419 Varani, 1999, Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17, Proc. Natl. Acad. Sci. USA, 96, 8229, 10.1073/pnas.96.14.8229 Vermersch, 1995, Cortical mapping of Alzheimer pathology in brains of aged non-demented subjects, Prog. Neuropsychopharmacol. Biol. Psychiatry, 19, 1035, 10.1016/0278-5846(95)00195-6 Vermersch, 1993, Dementia in Parkinson’s disease: biochemical evidence for cortical involvement using the immunodetection of abnormal Tau proteins, Ann. Neurol., 33, 445, 10.1002/ana.410330506 Vermersch, 1992, Presence of abnormally phosphorylated Tau proteins in the entorhinal cortex of aged non-demented subjects, Neurosci. Lett., 144, 143, 10.1016/0304-3940(92)90736-Q Vermersch, 1992, Mapping of neurofibrillary degeneration in Alzheimer’s disease: evaluation of heterogeneity using the quantification of abnormal tau proteins, Acta Neuropathol., 85, 48, 10.1007/BF00304633 Vermersch, 1994, Biochemical mapping of neurofibrillary degeneration in a case of progressive supranuclear palsy: evidence for general cortical involvement, Acta Neuropathol., 87, 572, 10.1007/BF00293317 Vermersch, 1996, Specific tau variants in the brains of patients with myotonic dystrophy, Neurology, 47, 711, 10.1212/WNL.47.3.711 Vincent, 1996, Mitotic mechanisms in Alzheimer’s disease?, J. Cell Biol., 132, 413, 10.1083/jcb.132.3.413 Vulliet, 1992, Proline-directed phosphorylation of human Tau protein, J. Biol. Chem., 267, 22570, 10.1016/S0021-9258(18)41710-3 Wakabayashi, 1998, Accumulation of alpha-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy, Acta Neuropathol., 96, 445, 10.1007/s004010050918 Wakabayashi, 1997, NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson’s disease, Neurosci. Lett., 239, 45, 10.1016/S0304-3940(97)00891-4 Wakabayashi, 1994, Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations, Acta Neuropathol., 87, 545, 10.1007/BF00293314 Wang, 1996, Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer’s disease, Nature Med., 2, 871, 10.1038/nm0896-871 Weingarten, 1975, A protein factor essential for microtubule assembly, Proc. Natl. Acad. Sci. USA, 72, 1858, 10.1073/pnas.72.5.1858 Wijker, 1996, Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21, Hum. Mol. Genet., 5, 151, 10.1093/hmg/5.1.151 Wilhelmsen, 1994, Localization of disinhibition–dementia–parkinsonism–amyotrophy complex to 17q21-22, Am. J. Hum. Genet., 55, 1159 Wille, 1992, Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro, J. Cell Biol., 118, 573, 10.1083/jcb.118.3.573 Wilson, 1997, Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer’s disease, Am. J. Pathol., 150, 2181 Wisniewski, 1989, Neuropathological diagnosis of Alzheimer disease, J. Neuropathol. Exp. Neurol., 48, 606, 10.1097/00005072-198911000-00001 Yamagishi, 1994, Pathology of olfactory mucosa in patients with Alzheimer’s disease, Ann. Otol. Rhinol. Laryngol., 103, 421, 10.1177/000348949410300601 Yamamoto, 1995, Dephosphorylation of fetal-tau and paired helical filaments-tau by protein phosphatases 1 and 2A and calcineurin, J. Biochem., 118, 1224, 10.1093/oxfordjournals.jbchem.a125011 Yamamoto, 1988, Dephosphorylation of microtubule proteins by brain protein phosphatases 1 and 2A, and its effect on microtubule assembly, J. Neurochem., 50, 1614, 10.1111/j.1471-4159.1988.tb03051.x Yan, 1995, Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide, Nature Med., 1, 693, 10.1038/nm0795-693 Yang, 1997, Tau released from paired helical filaments with formic acid or guanidine is susceptible to calpain-mediated proteolysis, J. Neurochem., 69, 1548, 10.1046/j.1471-4159.1997.69041548.x Yang, 1995, Calpain-induced proteolysis of normal human tau and tau associated with paired helical filaments, Eur. J. Biochem., 233, 9, 10.1111/j.1432-1033.1995.009_1.x Yen, 1999, Fibrillogenesis of tau: insights from tau missense mutations in FTDP-17, Brain Pathol., 9, 695, 10.1111/j.1750-3639.1999.tb00551.x Yin, 1995, Changes in the microtubule proteins in the developing and transected spinal cords of the bullfrog tadpole: induction of microtubule-associated protein 2C and enhanced levels of Tau and tubulin in regenerating central axons, Neuroscience, 67, 763, 10.1016/0306-4522(95)00042-H Zemaitaitis, 1999, Transglutaminase-induced crosslinking of tau protein in progressive supranuclear palsy, Soc. Neurosci. Abstr., 25, 1095 Zheng-Fischhofer, 1998, Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation, Eur. J. Biochem., 252, 542, 10.1046/j.1432-1327.1998.2520542.x