A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology
Tomonori Kobayashi MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorSatoru Ota MD
Department of Neurology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo
Search for more papers by this authorKuniaki Tanaka MD
Department of Psychiatry, Tokyo Metropolitan Tama Geriatric Hospital, Tokyo
Search for more papers by this authorYuji Ito MD
Department of Pathology, Tokyo Metropolitan Tama Geriatric Hospital, Tokyo
Search for more papers by this authorMasato Hasegawa PhD
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo
Search for more papers by this authorYuri Umeda BS
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo
Search for more papers by this authorYumiko Motoi MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorMasashi Takanashi MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorMasahiro Yasuhara MD
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorMidori Anno MD
Department of Neurology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo
Search for more papers by this authorYoshikuni Mizuno MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorCorresponding Author
Hideo Mori MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, JapanSearch for more papers by this authorTomonori Kobayashi MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorSatoru Ota MD
Department of Neurology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo
Search for more papers by this authorKuniaki Tanaka MD
Department of Psychiatry, Tokyo Metropolitan Tama Geriatric Hospital, Tokyo
Search for more papers by this authorYuji Ito MD
Department of Pathology, Tokyo Metropolitan Tama Geriatric Hospital, Tokyo
Search for more papers by this authorMasato Hasegawa PhD
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo
Search for more papers by this authorYuri Umeda BS
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo
Search for more papers by this authorYumiko Motoi MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorMasashi Takanashi MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorMasahiro Yasuhara MD
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorMidori Anno MD
Department of Neurology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo
Search for more papers by this authorYoshikuni Mizuno MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorCorresponding Author
Hideo Mori MD
Department of Neurology, Juntendo University School of Medicine, Tokyo
Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, JapanSearch for more papers by this authorAbstract
We report a novel mutation of tau (L266V missense mutation in exon 9) which may cause a type of familial frontotemporal dementia. The brain of a patient showed Pick body–like inclusions and unique tau-positive, argyrophilic astrocytes with stout filaments and naked, round, or irregular argyrophilic inclusions with deposits of both three-repeat and four-repeat tau. Recombinant tau with a L266V mutation showed a reduced ability to promote microtubule assembly, which may be the primary effect of the mutation. Ann Neurol 2003;53:000–000
References
- 1 McKhann GM, Albert MS, Grossman M, et al. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch Neurol 2001; 58: 1803–1809.
- 2 Kobayashi T, Mori H, Okuma Y, et al. Contrasting genotypes of the tau gene in two phenotypically distinct patients with P301L mutation of frontotemporal dementia and parkinsonism linked to chromosome 17. J Neurol 2002; 249: 669–675.
- 3 Goedert M, Spillantini MG, Cairns NJ, et al. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 1992; 8: 159–168.
- 4 Hayashi S, Toyoshima Y, Hasegawa M, et al. Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Ann Neurol 2002; 51: 525–530.
- 5 Hasegawa M, Smith MJ, Goedert M. Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett 1998; 437: 207–210.
- 6 Ishiguro K, Sato K, Takamatsu M, et al. Analysis of phosphorylation of tau with antibodies specific for phosphorylation sites. Neurosci Lett 1995; 202: 81–84.
- 7 Baker M, Litvan I, Houlden H, et al. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 1999; 8: 711–715.
- 8 Spillantini MG, Crowther RA, Kamphorst W, et al. Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am J Pathol 1998; 153: 1359–1363.
- 9 Rizzini C, Goedert M, Hodges JR, et al. Tau gene mutation K257T causes a tauopathy similar to Pick's disease. J Neuropathol Exp Neurol 2000; 59: 990–1001.
- 10 Ikeda K, Akiyama H, Arai T, et al. Pick-body-like inclusions in corticobasal degeneration differ from Pick bodies in Pick's disease. Acta Neuropathol (Berl) 2002; 103: 115–118.
- 11 Seubert P, Mawal-Dewan M, Barbour R, et al. Detection of phosphorylated Ser262 in fetal tau, adult tau, and paired helical filament tau. J Biol Chem 1995; 270: 18917–18922.
- 12 Rosso SM, van Herpen E, Deelen W, et al. A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease. Ann Neurol 2002; 51: 373–376.
- 13 Neumann M, Schulz-Schaeffer W, Crowther RA, et al. Pick's disease associated with the novel Tau gene mutation K369I. Ann Neurol 2001; 50: 503–513.
- 14 Murrell JR, Spillantini MG, Zolo P, et al. Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol 1999; 58: 1207–1226.
- 15 Komori T. Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Brain Pathol 1999; 9: 663–679.
- 16 Delacourte A, Robitaille Y, Sergeant N, et al. Specific pathological Tau protein variants characterize Pick's disease. J Neuropathol Exp Neurol 1996; 55: 159–168.
- 17 Hong M, Zhukareva V, Vogelsberg-Ragaglia V, et al. Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science 1998; 282: 1914–1917.
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