Frontotemporal dementia with parkinsonism linked to Chromosome 17

doi:10.1017/CBO9780511544873.036

35 - Frontotemporal dementia with parkinsonism linked to Chromosome 17

from Part VI - Other Dementias

Published online by Cambridge University Press: 04 August 2010

M. Flint Beal ,

Anthony E. Lang and

Albert C. Ludolph

Mark S. Forman ,

Virginia M.-Y. Lee and

John Q. Trojanowski

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M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Mark S. Forman: Affiliation:
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine University of Pennsylvania, PA, USA
Virginia M.-Y. Lee: Affiliation:
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine University of Pennsylvania, PA, USA
John Q. Trojanowski: Affiliation:
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine University of Pennsylvania, PA, USA

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Summary

Introduction

A variety of sporadic and familial neurodegenerative disorders, characterized clinically by dementia and/or motor dysfunction, demonstrate intracellular accumulations of filamentous material composed of the microtubule-associated protein (MAP) tau (See chapters 29, ‘Neuropathology of Alzheimer's disease’, 34, ‘Pick's and other frontotemporal dementias’, 44, ‘Progressive supranuclear palsy’, and 45, ‘Corticobasal degeneration’). The term ‘tauopathies’ was coined to refer to this seemingly heterogeneous group of neurodegenerative disorders with filamentous tau deposits as their predominant histopathological feature. The progressive accumulation of filamentous tau inclusions in the absence of other disease-specific neuropathological abnormalities provided circumstantial evidence implicating tau dysfunction in disease onset and/or progression. However, the discovery of pathogenic tau mutations in a heterogeneous group of disorders termed frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) provided unequivocal confirmation of the central role of tau abnormalities in the etiology of neurodegenerative disorders (Foster et al., 1997; Poorkaj et al., 1998; Hutton et al., 1998; Spillantini et al., 1998c). This seminal finding has opened novel areas of investigation into the pathophysiologic mechanisms of tau dysfunction and the relationship of tau abnormalities to brain degeneration.

Familial frontotemporal dementia

In 1892, Arnold Pick described a woman with lobar brain atrophy, who presented clinically with presenile dementia and aphasia (Pick, 1892). Thus, this was the first description of what is now classified clinically as frontotemporal dementia (FTD) (McKhann et al., 2001).

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 494 - 511

DOI: https://doi.org/10.1017/CBO9780511544873.036 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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References

Andreadis, A., Brown, W. M. & Kosik, K. S. (1992). Structure and novel exons of the human tau gene. Biochemistry, 31, 10626–33CrossRef Google Scholar PubMed

Arawaka, S., Usami, M., Sahara, N., Schellenberg, G. D., Lee, G. & Mori, H. (1999). The tau mutation (val337met) disrupts cytoskeletal networks of microtubules. Neuroreport, 10, 993–7CrossRef Google Scholar PubMed

Arima, K., Kowalska, A., Hasegawa, M.et al. (2000). Two brothers with frontotemporal dementia and parkinsonism with an N279K mutation of the tau gene. Neurology, 54, 1787–95CrossRef Google Scholar PubMed

Arrasate, M., Perez, M., Armas-Portela, R. & Avila, J. (1999). Polymerization of tau peptides into fibrillar structures. The effect of FTDP-17 mutations. FEBS Lett., 446, 199–202CrossRef Google Scholar PubMed

Ashworth, A., Lloyd, S., Brown, J.et al. (1999). Molecular genetic characterization of frontotemporal dementia on chromosome 3. Dement. Geriatr. Cogn. Disord., 10 (Suppl 1), 93–101CrossRef Google Scholar

Baker, M., Kwok, J. B., Kucera, S.et al. (1997). Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21–22. Ann. Neurol., 42, 794–8CrossRef Google Scholar

Barghorn, S., Zheng-Fischhofer, Q., Ackmann, M.et al. (2000). Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias. Biochemistry, 39, 11714–21CrossRef Google Scholar PubMed

Biernat, J., Gustke, N., Drewes, G., Mandelkow, E. M. & Mandelkow, E. (1993). Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron, 11, 153–63CrossRef Google Scholar PubMed

Billingsley, M. L. & Kincaid, R. L. (1997). Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem. J, 323, 577–91CrossRef Google Scholar PubMed

Binder, L. I., Frankfurter, A. & Rebhun, L. I. (1985). The distribution of tau in the mammalian central nervous system. J. Cell. Biol., 101, 1371–8CrossRef Google Scholar PubMed

Bird, T. D., Wijsman, E. M., Nochlin, D.et al. (1997). Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD. Neurology, 48, 949–54CrossRef Google Scholar PubMed

Bird, T. D., Nochlin, D., Poorkaj, P.et al. (1999). A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain, 122, 741–756CrossRef Google Scholar

Bramblett, G. T., Goedert, M., Jakes, R., Merrick, S. E., Trojanowski, J. Q. & Lee, V. M.-Y. (1993). Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron, 10, 1089–99CrossRef Google Scholar PubMed

Brown, J. (1998). Chromosome 3-linked frontotemporal dementia. Cell Mol. Life Sci., 54, 925–7CrossRef Google Scholar PubMed

Buée, L., Bussière, T., Buée-Scherrer, V., Delacourte, A. & Hof, P. R. (2000). Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Rev., 33, 1–36CrossRef Google Scholar PubMed

Bugiani, O., Murrell, J. R., Giaccone, G.et al. (1999). Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J. Neuropathol. Exp. Neurol., 58, 667–77CrossRef Google Scholar

Butner, K. A. & Kirschner, M. W. (1991). Tau protein binds to microtubules through a flexible array of distributed weak sites. J. Cell Biol., 115, 717–30CrossRef Google Scholar PubMed

Chow, T. W., Miller, B. L., Hayashi, V. N. & Geschwind, D. H. (1999). Inheritance of frontotemporal dementia. Arch. Neurol., 56, 817–22CrossRef Google Scholar PubMed

Clark, L. N., Poorkaj, P., Wszolek, Z.et al. (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, 13103–7CrossRef Google Scholar PubMed

Cleveland, D. W., Hwo, S. Y. & Kirschner, M. W. (1977). Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J. Mol. Biol., 116, 207–25CrossRef Google Scholar PubMed

Connell, J. W., Gibb, G. M., Betts, J. C.et al. (2001). Effects of FTDP-17 mutations on the in vitro phosphorylation of tau by glycogen synthase kinase 3beta identified by mass spectrometry demonstrate certain mutations exert long-range conformational changes. FEBS Lett., 493, 40–4CrossRef Google Scholar PubMed

Couchie, D., Mavilia, C., Georgieff, I. S., Liem, R. K., Shelanski, M. L. & Nunez, J. (1992). Primary structure of high molecular weight tau present in the peripheral nervous system. Proc. Natl Acad. Sci., USA, 89, 4378–81CrossRef Google Scholar PubMed

D'Souza, I. & Schellenberg, D. (2000). Determinants of 4 repeat tau expression: Coordination between enhancing and inhibitory splicing sequences for exon 10 inclusion. J. Biol. Chem., 275, 17700–9CrossRef Google Scholar PubMed

D'Souza, I., Poorkaj, P., Hong, M.et al. (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, 5598–603CrossRef Google Scholar PubMed

Dayanandan, R., Slegtenhorst, M., Mack, T. G.et al. (1999). Mutations in tau reduce its microtubule binding properties in intact cells and affect its phosphorylation. FEBS Lett., 446, 228–32CrossRef Google Scholar PubMed

Delisle, M. B., Murrell, J. R., Richardson, R.et al. (1999). A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy. Acta Neuropathol.(Berl), 98, 62–77CrossRef Google Scholar PubMed

DeTure, M., Ko, L. W., Yen, S.et al. (2000). Missense tau mutations identified in FTDP-17 have a small effect on tau-microtubule interactions. Brain Res., 853, 5–14CrossRef Google Scholar PubMed

Drechsel, D. N., Hyman, A. A., Cobb, M. H. & Kirschner, M. W. (1992). Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol. Biol. Cel., 3, 1141–54CrossRef Google Scholar PubMed

Dumanchin, C., Camuzat, A., Campion, D.et al. (1998). Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Hum. Mol. Genet., 7, 1825–9CrossRef Google Scholar PubMed

Fabre, S. F., Forsell, C., Viitanen, M.et al. (2001). Clinic-based cases with frontotemporal dementia show increased cerebrospinal fluid tau and high apolipoprotein E epsilon4 frequency, but no tau gene mutations. Exp. Neurol., 168, 413–18CrossRef Google Scholar PubMed

Foster, N. L., Wilhelmsen, K., Sima, A. A., Jones, M. Z., D'Amato, C. J. & Gilman, S. (1997). Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Ann. Neurol., 41, 706–15CrossRef Google Scholar PubMed

Frappier, T., Liang, N. S., Brown, K.et al. (1999). Abnormal microtubule packing in processes of SF9 cells expressing the FTDP-17 V337M tau mutation. FEBS Lett., 455, 262–6CrossRef Google Scholar PubMed

Furukawa, K., D'Souza, I., Crudder, C. H.et al. (2000). Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism. Neuroreport, 11, 57–60CrossRef Google Scholar PubMed

Gamblin, T. C., King, M. E., Dawson, H.et al. (2000). In vitro polymerization of tau protein monitored by laser light scattering: method and application to the study of FTDP-17 mutants. Biochemistry, 39, 6136–44CrossRef Google Scholar

Gao, Q. S., Memmott, J., Lafyatis, R., Stamm, S., Screaton, G. & Andreadis, A. (2000). Complex regulation of tau exon 10, whose missplicing causes frontotemporal dementia. J. Neurochem., 74, 490–500CrossRef Google Scholar PubMed

Geschwind, D. H., Robidoux, J., Alarcon, M.et al. (2001). Dementia and neurodevelopmental predisposition: cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia. Ann. Neurol., 50, 741–6CrossRef Google Scholar PubMed

Goedert, M. & Jakes, R. (1990). Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J, 9, 4225–30Google Scholar PubMed

Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., and Klug, A. (1988). Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc. Natl Acad. Sci., USA, 85, 4051–5CrossRef Google Scholar PubMed

Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D. & Crowther, R. A. (1989a). Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron, 3, 519–26CrossRef Google Scholar

Goedert, M., Spillantini, M. G., Potier, M. C., Ulrich, J. & Crowther, R. A. (1989b). 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, 393–9Google Scholar

Goedert, M., Jakes, R. & Crowther, R. A. (1999a). Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments. FEBS Lett., 450, 306–11CrossRef Google Scholar

Goedert, M., Spillantini, M. G., Crowther, R. A.et al. (1999b). Tau gene mutation in familial progressive subcortical gliosis. Nat. Med., 5, 454–7CrossRef Google Scholar

Goedert, M., Satumtira, S., Jakes, R.et al. (2000). Reduced binding of protein phosphatase 2A to tau protein with frontotemporal dementia and parkinsonism linked to chromosome 17 mutations. J. Neurochem., 75, 2155–62CrossRef Google Scholar PubMed

Goode, B. L. & Feinstein, S. C. (1994). Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau. J. Cell Biol., 124, 769–82CrossRef Google Scholar PubMed

Goode, B. L., Denis, P. E., Panda, D.et al. (1997). Functional interactions between the proline-rich and repeat regions of tau enhance microtubule binding and assembly. Mol. Biol. Cel., 8, 353–65CrossRef Google Scholar

Götz, J. (2001). Tau and transgenic animal models. Brain Res. Rev., 35, 266–86CrossRef Google Scholar PubMed

Götz, J., Chen, F., Barmettler, R. & Nitsch, R. M. (2001a). Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem., 276, 529–34CrossRef Google Scholar

Götz, J., Chen, F., Dorpe, J. & Nitsch, R. M. (2001b). Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Abeta 42 fibrils. Science, 293, 1491–5CrossRef Google Scholar

Götz, J., Tolnay, M., Barmettler, R., Chen, F., Probst, A. & Nitsch, R. M. (2001c). Oligodendroglial tau filament formation in transgenic mice expressing G272V tau. Eur. J. Neurosci., 13, 2131–40CrossRef Google Scholar

Grover, A., Houlden, H., Baker, M.et al. (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, 15134–43CrossRef Google Scholar PubMed

Grover, A., DeTure, M., Yen, S. H. & Hutton, M. (2002). Effects on splicing and protein function of three mutations in codon N296 of tau in vitro. Neurosci. Lett., 323, 33–6CrossRef Google Scholar PubMed

Hall, G. F., Yao, J. & Lee, G. (1997). Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ. Proc. Natl Acad. Sci., USA, 94, 4733–8CrossRef Google Scholar PubMed

Hall, G. F., Chu, B., Lee, G. & Yao, J. (2000). Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease. J. Cell Sci., 113 (8), 1373–87Google Scholar

Hasegawa, M., Jakes, R., Crowther, R. A., Lee, V. M.-Y., Ihara, Y. & Goedert, M. (1996). Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein. FEBS Lett., 384, 25–30CrossRef Google Scholar PubMed

Hasegawa, M., Smith, M. J. & Goedert, M. (1998). Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett., 437, 207–10CrossRef Google Scholar PubMed

Hasegawa, M., Smith, M. J., Iijima, M., Tabira, T. & Goedert, M. (1999). FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10. FEBS Lett., 443, 93–6CrossRef Google Scholar PubMed

Hayashi, S., Toyoshima, Y., Hasegawa, M.et al. (2002). Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Ann. Neurol., 51, 525–30CrossRef Google Scholar PubMed

Heutink, P., Stevens, M., Rizzu, P.et al. (1997). Hereditary frontotemporal dementia is linked to chromosome 17q21–q22: a genetic and clinicopathological study of three Dutch families. Ann. Neurol., 41, 150–9CrossRef Google Scholar PubMed

Himmler, A., Drechsel, D., Kirschner, M. W. & Martin, D. W. Jr. (1989). Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. Mol. Cell Biol., 9, 1381–8CrossRef Google Scholar PubMed

Ho, L., Xiang, Z., Mukherjee, P.et al. (2001). Gene expression profiling of the tau mutant (P301L) transgenic mouse brain. Neurosci. Lett., 310, 1–4CrossRef Google Scholar PubMed

Hoffmann, R., Lee, V. M.-Y., Leight, S., Varga, I. & Otvos, L. Jr. (1997). Unique Alzheimer's disease paired helical filament specific epitopes involve double phosphorylation at specific sites. Biochemistry, 36, 8114–24CrossRef Google Scholar PubMed

Hong, M., Zhukareva, V., Vogelsberg-Ragaglia, V.et al. (1998). Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science, 282, 1914–17CrossRef Google Scholar PubMed

Hong, M., Trojanowski, J. Q. & Lee, V. M.-Y., (2000). Tau-based neurofibrillary lesions. In: Neurodegenerative Dementias, ed. C. M. Clark & J. Q. Trojanowski, pp. 161–75. New York: McGrawHill

Hosler, B. A., Siddique, T., Sapp, P. C.et al. (2000). Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21–q22. J. Am. Med. Assoc., 284, 1664–9CrossRef Google Scholar PubMed

Houlden, H., Baker, M., Adamson, J.et al. (1999). Frequency of tau mutations in three series of non-Alzheimer's degenerative dementia. Ann. Neurol., 46, 243–83.0.CO;2-L>CrossRef Google Scholar PubMed

Hulette, C. M., Pericak-Vance, M. A., Roses, A. D.et al. (1999). Neuropathological features of frontotemporal dementia and parkinsonism linked to chromosome 17q21–22 (FTDP-17): Duke Family 1684. J. Neuropathol. Exp. Neurol., 58, 859–66CrossRef Google Scholar PubMed

Hutton, M., Lendon, C. L., Rizzu, P.et al. (1998). Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature, 393, 702–5CrossRef Google Scholar PubMed

Iijima, M., Tabira, T., Poorkaj, P.et al. (1999). A distinct familial presenile dementia with a novel missense mutation in the tau gene. Neuroreport, 10, 497–501CrossRef Google Scholar PubMed

Iseki, E., Matsumura, T., Marui, W.et al. (2001). Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in exon 10 of the tau gene and a widespread tau accumulation in glial cells. Acta Neuropathol., 102, 285–92Google Scholar

Jackson, J. R., Wiedau-Pazos, M., Sang, T.-K.et al. (2002). Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron, 34, 509–19CrossRef Google Scholar PubMed

Janssen, J. C., Warrington, E. K., Morris, H. R.et al. (2002). Clinical features of frontotemporal dementia due to the intronic tau 10(+16) mutation. Neurology, 58, 1161–8CrossRef Google Scholar PubMed

Jiang, Z., Cote, J., Kwon, J. M., Goate, A. M. & Wu, J. Y. (2000). Aberrant splicing of tau pre-mRNA caused by intronic mutations associated with the inherited dementia frontotemporal dementia with parkinsonism linked to chromosome 17. Mol. Cell Biol., 20, 4036–48CrossRef Google Scholar PubMed

Jicha, G. A., Rockwood, J. M., Berenfeld, B., Hutton, M. & Davies, P. (1999). Altered conformation of recombinant frontotemporal dementia-17 mutant tau proteins. Neurosci. Lett., 260, 153–6CrossRef Google Scholar PubMed

Kawai, J., Sasahara, M., Hazama, F.et al. (1993). Pallidonigroluysian degeneration with iron deposition: a study of three autopsy cases. Acta Neuropathol. (Berl.), 86, 609–16CrossRef Google Scholar PubMed

Kiuchi, A., Otsuka, N., Namba, Y., Nakano, I. & Tomonaga, M. (1991). Presenile appearance of abundant Alzheimer's neurofibrillary tangles without senile plaques in the brain in myotonic dystrophy. Acta Neuropathol. (Berl.), 82, 1–5CrossRef Google Scholar PubMed

Knopman, D. S., Mastri, A. R., Frey, W. H., Sung, J. H. & Rustan, T. (1990). Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology, 40, 251–6CrossRef Google Scholar PubMed

Kodama, K., Okada, S., Iseki, E.et al. (2000). Familial frontotemporal dementia with a P301L tau mutation in Japan. J. Neurol. Sci., 176, 57–64CrossRef Google Scholar PubMed

Komori, T. (1999). Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Brain Pathol., 9, 663–79CrossRef Google Scholar PubMed

Kovach, M. J., Waggoner, B., Leal, S. M.et al. (2001). Clinical delineation and localization to chromosome 9p13.3–p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia. Mol. Genet. Metab., 74, 458–75CrossRef Google Scholar PubMed

Lee, G., Neve, R. L. & Kosik, K. S. (1989). The microtubule binding domain of tau protein. Neuron, 2, 1615–24CrossRef Google Scholar PubMed

Lee, V. M.-Y., Goedert, M. & Trojanowski, J. Q. (2001). Neurodegenerative tauopathies. Ann. Rev. Neurosci., 24, 1121–59CrossRef Google Scholar PubMed

Lendon, C. L., Lynch, T., Norton, J.et al. (1998). Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to 17q21–22. Neurology, 50, 1546–55CrossRef Google Scholar PubMed

Lewis, J., McGowan, E., Rockwood, J.et al. (2000). Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet., 25, 402–5CrossRef Google Scholar PubMed

Lewis, J., Dickson, D. W., Lin, W. L.et al. (2001). Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science, 293, 1487–91CrossRef Google Scholar PubMed

Lippa, C. F., Zhukareva, V., Kawarai, T.et al. (2000). Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation. Ann. Neurol., 48, 850–83.0.CO;2-V>CrossRef Google Scholar

LoPresti, P., Szuchet, S., Papasozomenos, S. C., Zinkowski, R. P. & Binder, L. I. (1995). Functional implications for the microtubule-associated protein tau: localization in oligodendrocytes. Proc. Natl Acad. Sci., USA, 92, 10369–73CrossRef Google Scholar PubMed

Lund and Manchester Groups (1994). Clinical and neuropathological criteria for frontotemporal dementia. J. Neurol. Neurosurg. Psychiatr., 57, 416–18CrossRef

Matsumura, N., Yamazaki, T. & Ihara, Y. (1999). Stable expression in Chinese hamster ovary cells of mutated tau genes causing frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Am. J. Pathol., 154, 1649–56CrossRef Google Scholar

McKhann, G. M., Albert, M. S., Grossman, M., Miller, B., Dickson, D. & Trojanowski, J. Q. (2001). Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch. Neurol., 58, 1803–9CrossRef Google Scholar PubMed

Mirra, S. S., Murrell, J. R., Gearing, M.et al. (1999). Tau pathology in a family with dementia and a P301L mutation in tau. J. Neuropathol. Exp. Neurol., 58, 335–45CrossRef Google Scholar

Miyamoto, K., Kowalska, A., Hasegawa, M.et al. (2001). Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene. Ann. Neurol., 50, 117–20CrossRef Google Scholar PubMed

Miyasaka, T., Morishima-Kawashima, M., Ravid, R., Kamphorst, W., Nagashima, K. & Ihara, Y. (2001). Selective deposition of mutant tau in the FTDP-17 brain affected by the P301L mutation. J. Neuropathol. Exp. Neurol., 60, 872–84CrossRef Google Scholar PubMed

Morris, H. R., Perez-Tur, J., Janssen, J. C.et al. (1999). Mutation in the tau exon 10 splice site region in familial frontotemporal dementia. Ann. Neurol., 45, 270–13.0.CO;2-2>CrossRef Google Scholar PubMed

Morris, H. R., Khan, M. N., Janssen, J. C.et al. (2001). The genetic and pathological classification of familial frontotemporal dementia. Arch. Neurol., 58, 1813–16CrossRef Google Scholar PubMed

Murrell, J. R., Koller, D., Foroud, T.et al. (1997). Familial multiple-system tauopathy with presenile dementia is localized to chromosome 17. Am. J. Hum. Genet., 61, 1131–8CrossRef Google Scholar PubMed

Murrell, J. R., Spillantini, M. G., Zolo, P.et al. (1999). Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J. Neuropathol. Exp. Neurol., 58, 1207–26CrossRef

Nacharaju, P., Lewis, J., Easson, C., Yen, S., Hackett, J., Hutton, M. & Yen, S. H. (1999). Accelerated filament formation from tau protein with specific FTDP-17 missense mutations. FEBS Lett., 447, 195–9CrossRef Google Scholar PubMed

Nagiec, E. W., Sampson, K. E. & Abraham, I. (2001). Mutated tau binds less avidly to microtubules than wildtype tau in living cells. J. Neurosci. Res., 63, 268–753.0.CO;2-E>CrossRef Google Scholar PubMed

Nasreddine, Z. S., Loginov, M., Clark, L. N.et al. (1999). From genotype to phenotype: a clinical pathological, and biochemical investigation of frontotemporal dementia and parkinsonism (FTDP-17) caused by the P301L tau mutation. Ann. Neurol., 45, 704–153.0.CO;2-X>CrossRef Google Scholar PubMed

Neumann, M., Schulz-Schaeffer, W., Crowther, R. A.et al. (2001). Pick's disease associated with the novel Tau gene mutation K369I. Ann. Neurol., 50, 503–13CrossRef Google Scholar PubMed

Neve, R. L., Harris, P., Kosik, K. S., Kurnit, D. M. & Donlon, T. A. (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, 271–80Google Scholar PubMed

Pastor, P., Pastor, E., Carnero, C.et al. (2001). Familial atypical progressive supranuclear palsy associated with homozygosity for the delN296 mutation in the tau gene. Ann. Neurol., 49, 263–73.0.CO;2-K>CrossRef Google Scholar PubMed

Perez, M., Lim, F., Arrasate, M. & Avila, J. (2000). The FTDP-17-linked mutation R406W abolishes the interaction of phosphorylated tau with microtubules. J. Neurochem., 74, 2583–9CrossRef Google Scholar PubMed

Pick, A. (1892). Über die Bejiehungen der senilen Hirnatrophie zur Aphasie. Prager. Med. Wochenschr., 17, 165–7Google Scholar

Pickering-Brown, S., Baker, M., Yen, S. H.et al. (2000). Pick's disease is associated with mutations in the tau gene. Ann. Neurol., 48, 859–673.0.CO;2-1>CrossRef Google Scholar PubMed

Pickering-Brown, S. M., Richardson, A. M., Snowden, J. S.et al. (2002). Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain, 125, 732–51CrossRef Google Scholar PubMed

Poorkaj, P., Bird, T. D., Wijsman, E.et al. (1998). Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol., 43, 815–25CrossRef Google Scholar PubMed

Poorkaj, P., Grossman, M., Steinbart, E.et al. (2001). Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia. Arch. Neurol., 58, 383–7CrossRef Google Scholar PubMed

Poorkaj, P., Muma, N. A., Zhukareva, V.et al. (2002). An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann. Neurol., 52, 511–16CrossRef Google Scholar

Reed, L. A., Grabowski, T. J., Schmidt, M. L.et al. (1997). Autosomal dominant dementia with widespread neurofibrillary tangles. Ann. Neurol., 42, 564–72CrossRef Google Scholar PubMed

Reed, L. A., Schmidt, M. L., Wszolek, Z. K.et al. (1998). The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia (‘pallido-ponto-nigral degeneration’). J. Neuropathol. Exp. Neurol., 57, 588–601CrossRef Google Scholar

Reed, L. A., Wszolek, Z. K. & Hutton, M. (2001). Phenotypic correlations in FTDP-17. Neurobiol. Agin., 22, 89–107CrossRef Google Scholar PubMed

Rizzini, C., Goedert, M., Hodges, J. R.et al. (2000). Tau gene mutation K257T causes a tauopathy similar to Pick's disease. J. Neuropathol. Exp. Neurol., 59, 990–1001CrossRef Google Scholar PubMed

Rizzu, P., Swieten, J. C., Joosse, M.et al. (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, 414–21CrossRef Google Scholar

Rizzu, P., Joosse, M., Ravid, R.et al. (2000). Mutation-dependent aggregation of tau protein and its selective depletion from the soluble fraction in brain of P301L FTDP-17 patients. Hum. Mol. Genet., 9, 3075–82CrossRef Google Scholar PubMed

Rosso, S. M., Kamphorst, W., Graaf, B.et al. (2001). Familial frontotemporal dementia with ubiquitin-positive inclusions is linked to chromosome 17q21–22. Brain, 124, 1948–57CrossRef Google Scholar PubMed

Rosso, S. M., Kamphorst, W., Ravid, R. & Swieten, J. C. (2000). Coexistent tau and amyloid pathology in hereditary frontotemporal dementia with tau mutations. Ann. NY. Acad. Sci., 920, 115–19CrossRef Google Scholar PubMed

Rosso, S. M., Herpen, E., Deelen, W.et al. (2002). A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease. Ann. Neurol., 51, 373–6CrossRef Google Scholar PubMed

Sahara, N., Tomiyama, T. & Mori, H. (2000). Missense point mutations of tau to segregate with FTDP-17 exhibit site-specific effects on microtubule structure in COS cells: a novel action of R406W mutation. J. Neurosci. Res., 60, 380–73.0.CO;2-5>CrossRef Google Scholar PubMed

Saito, Y., Geyer, A., Sasaki, R.et al. (2002). Early-onset, rapidly progressive familial tauopathy with R406W mutation. Neurology, 58, 811–13CrossRef Google Scholar PubMed

Sanders, J., Schenk, V. & Veen, P. (1939). A family with Pick's disease. Veerhandelingen de Koninklijke Nederlandse Akadamie van WetenschappenGoogle Scholar

Schenk, V. (1959). Re-examination of a family with Pick's disease. Ann. Hum. Genet., 23, 325–33CrossRef Google Scholar PubMed

Senapathy, P., Shapiro, M. B. & Harris, N. L. (1990). Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. Methods Enzymol., 183, 252–78CrossRef Google Scholar PubMed

Sergeant, N., Sablonniere, B., Schraen-Maschke, S.et al. (2001). Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1. Hum. Mol. Genet., 10, 2143–55CrossRef Google Scholar PubMed

Shin, R. W., Iwaki, T., Kitamoto, T. & Tateishi, J. (1991). Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab. Invest., 64, 693–702Google Scholar PubMed

Si, Z. H., Rauch, D. & Stoltzfus, C. M. (1998). The exon splicing silencer in human immunodeficiency virus type 1 Tat exon 3 is bipartite and acts early in spliceosome assembly. Mol. Cell Biol., 18, 5404–13CrossRef Google Scholar PubMed

Sperfeld, A. D., Collatz, M. B., Baier, H.et al. (1999). FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann. Neurol., 46, 708–153.0.CO;2-K>CrossRef Google Scholar PubMed

Spillantini, M. G., Crowther, R. A. & Goedert, M. (1996). Comparison of the neurofibrillary pathology in Alzheimer's disease and familial presenile dementia with tangles. Acta Neuropathol. (Berl.), 92, 42–8CrossRef Google Scholar PubMed

Spillantini, M. G., Bird, T. D. & Ghetti, B. (1998a). Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol., 8, 387–402CrossRef Google Scholar

Spillantini, M. G., Crowther, R. A., Kamphorst, W., Heutink, P. & Swieten, J. C. (1998b). Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am. J. Pathol., 153, 1359–63CrossRef Google Scholar

Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A. & Ghetti, B. (1998c). Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl Acad. Sci., USA, 95, 7737–41CrossRef Google Scholar

Spillantini, M. G., Yoshida, H., Rizzini, C.et al. (2000). A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies. Ann. Neurol., 48, 939–433.0.CO;2-1>CrossRef Google Scholar PubMed

Stanford, P. M., Halliday, G. M., Brooks, W. S.et al. (2000). Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations. Brain, 123, 880–93CrossRef Google Scholar PubMed

Stevens, M., Duijn, C. M., Kamphorst, W.et al. (1998). Familial aggregation in frontotemporal dementia. Neurology, 50, 1541–5CrossRef Google Scholar PubMed

Sumi, S. M., Bird, T. D., Nochlin, D. & Raskind, M. A. (1992). Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala. Neurology, 42, 120–7CrossRef Google Scholar PubMed

Tanaka, K., Watakabe, A. & Shimura, Y. (1994). Polypurine sequences within a downstream exon function as a splicing enhancer. Mol. Cell Biol., 14, 1347–54CrossRef Google Scholar PubMed

Tanaka, R., Kobayashi, T., Motoi, Y., Anno, M., Mizuno, Y. & Mori, H. (2000). A case of frontotemporal dementia with tau P301L mutation in the Far East. J. Neurol., 247, 705–7CrossRef Google Scholar PubMed

Tanemura, K., Akagi, T., Murayama, M.et al. (2001). Formation of filamentous tau aggregations in transgenic mice expressing V337M human tau. Neurobiol. Dis., 8, 1036–45CrossRef Google Scholar PubMed

Tanemura, K., Murayama, M., Akagi, T.et al. (2002). Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau. J. Neurosci., 22, 133–41CrossRef Google Scholar

Tolnay, M., Grazia, S. M., Rizzini, C., Eccles, D., Lowe, J. & Ellison, D. (2000). A new case of frontotemporal dementia and parkinsonism resulting from an intron 10 +3-splice site mutation in the tau gene: clinical and pathological features. Neuropathol. Appl. Neurobiol., 26, 368–78CrossRef Google Scholar PubMed

Swieten, J. C., Stevens, M., Rosso, S. M.et al. (1999). Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann. Neurol., 46, 617–263.0.CO;2-I>CrossRef Google Scholar PubMed

Varani, L., Hasegawa, M., Spillantini, M. G.et al. (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, 8229–34CrossRef Google Scholar PubMed

Vogelsberg-Ragaglia, V., Bruce, J., Richter-Landsberg, C.et al. (2000). Distinct FTDP-17 missense mutations in tau produce tau aggregates and other pathological phenotypes in transfected CHO cells. Mol. Biol. Cel., 11, 4093–104CrossRef Google Scholar PubMed

Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E. M. & Mandelkow, E. (2000). Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure. Proc. Natl Acad. Sci., USA, 97, 5129–34CrossRef Google Scholar

Bergen, M., Barghorn, S., Li, L.et al. (2001). Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J. Biol. Chem., 276, 48165–74CrossRef Google Scholar

Weingarten, M. D., Lockwood, A. H., Hwo, S. Y. & Kirschner, M. W. (1975). A protein factor essential for microtubule assembly. Proc. Natl Acad. Sci., USA, 72, 1858–62CrossRef Google Scholar PubMed

Wijker, M., Wszolek, Z. K., Wolters, E. C.et al. (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, 151–4CrossRef Google Scholar PubMed

Wilhelmsen, K. C., Lynch, T., Pavlou, E., Higgins, M. & Nygaard, T. G. (1994). Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21–22. Am. J. Hum. Genet., 55, 1159–65Google Scholar PubMed

Wittmann, C. W., Wszolek, M. F., Shulman, J. M.et al. (2001). Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science, 293, 711–14CrossRef Google Scholar PubMed

Yasuda, M., Kawamata, T., Komure, O.et al. (1999). A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration. Neurology, 53, 864–8CrossRef Google Scholar PubMed

Yasuda, M., Takamatsu, J., D'Souza, I.et al. (2000a). A novel mutation at position +12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTD-Kumamoto). Ann. Neurol., 47, 422–93.0.CO;2-G>CrossRef Google Scholar

Yasuda, M., Yokoyama, K., Nakayasu, T.et al. (2000b). A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation. Neurology, 55, 1224–7CrossRef Google Scholar

Yen, S., Easson, C., Nacharaju, P., Hutton, M. & Yen, S. H. (1999a). FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion. FEBS Lett., 461, 91–5CrossRef Google Scholar

Yen, S. H., Hutton, M., DeTure, M., Ko, L. W. & Nacharaju, P. (1999b). Fibrillogenesis of tau: insights from tau missense mutations in FTDP-17. Brain Pathol., 9, 695–705CrossRef Google Scholar

Yoshida, H. & Ihara, Y. (1993). Tau in paired helical filaments is functionally distinct from fetal tau: assembly incompetence of paired helical filament-tau. J. Neurochem., 61, 1183–6CrossRef Google Scholar PubMed

Zheng-Fischhofer, Q., Biernat, J., Mandelkow, E. M., Illenberger, S., Godemann, R. & Mandelkow, E. (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, 542–52CrossRef Google Scholar PubMed

Zhukareva, V., Vogelsberg-Ragaglia, V., Deerlin, V. M.et al. (2001). Loss of brain tau defines novel sporadic and familial tauopathies with frontotemporal dementia. Ann. Neurol., 49, 165–753.0.CO;2-3>CrossRef Google Scholar PubMed