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Identification of posttranslational modification of the tau in paired helical filaments

Research Project

Project/Area Number 03102008
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Research InstitutionUniversity of Tokyo

Principal Investigator

IHARA Yasuo  Faculty of Medicine, University of Tokyo Prof., 医学部・脳研究施設脳病理, 教授 (60114386)

Co-Investigator(Kenkyū-buntansha) 森 啓  東京大学, 医学部(医), 助教授 (10159189)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥110,000,000 (Direct Cost: ¥110,000,000)
Fiscal Year 1993: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1992: ¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 1991: ¥80,000,000 (Direct Cost: ¥80,000,000)
KeywordsAlzheimer's disease / Paired helical flaments / tau / phosphorylation / proline-directed protein kinase / ubiquitin / アルツハイマ-病 / Alzheimer′s disease / Paired helical filaments / Phosphorylation / Ubiquitination / Fragmntation
Research Abstract

Paired helical filaments (PHF) are closely related to neuronal death and thus their complete elucidation should lead us to understanding of particular intracellular environmental alterations that cause neurons to die. I focused on the abnormal phosphorylation of PHF-tau because the phosphorylation could precede the PHF formation.
Two phosphorylation-dependent PHF polyclonals and two PHF monoclonals each of which has distinct specificity has been shown to recognize fetal tau but not adult tau. This observation led us to determine the phosphorylation sites in fetal tau as a first step. Fetal tau bears at most ten covalently bound phosphates, eight of which are proline-directed. The phosphorylation sites are roughly equal to those phosphorylated by cdk5 and GSK3beta. Two non proline-directed phosphorylated sites are found to be indeed the motifs for GSK3beta, when downstream proline-directed sites are phosphorylated.
We next attempted to determine the phosphorylation sites in PHF in a simil … More ar way. Major difficulaties were unusual resistance to many specific proteases and very poor recovery of phosphopeptides from a HPLC column, which was never experienced in fetal tau. PHF-tau is phosphorylated at most twenty One sites ; Ten are proline-directed, while eleven are non proline-directed. Most of the sites phosphorylated in fetal tau are also phosphorylated in PHF-tau, which explains those immunochemical similarities between PHF-tau and fetal tau. Overall, the phosphorylation of PHF can be considered to consist of fetal-type phosphorylation plus additional proline-directed and non proline-directed phosphorylation. Some of those non proline-directed sites correspond to the sites phosphorylated by cAMP-dependent protein kinase (PKA). Thus, the phosphorylation of PHF-tau would be mediated by multiple kinases, cdk5, GSK3beta, and possibly PKA.Those non proline-directed phosphorylation which distinguish PHF-tau from fetal tau may be important to the unusual characteristics of PHF-tau, including its assembly incompetence and protease resistance. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (98 results)

All Other

All Publications (98 results)

  • [Publications] Yamaguchi H et al.: "Amyloid β/A4 protein precursor is bound to neurofibrillary tangles in Alzheimer-type dementia." Brain Res. 537. 318-322 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H et al.: "Secondary deposition of β amyloid within extracellular neurofibrillary tangles in Alzheimer-type dementia." Am.J.Pathol.138. 699-705 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H et al.: "Extracellar neurofibrillary tangles associated with de generating neurites and neuropil threads in Alzheimer-type dementia." Acta Neuropathol.81. 603-609 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F et al.: "Differential expression of β amyloid protein precursor (APP) and tau mRNA in the aged human brain:Individual variability and correlation between APP-751 and four-repeat tau." J.Neuropathol.Exp.Neurol.50. 560-578 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morishima M et al.: "A possible fetal antigen of Mr 70,000 in neurofibrillary tangles." Brain Res.554. 316-320 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchida Y et al.: "The growth in-hibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein like protein." Neuron. 7. 337-347 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ihara Y et al.: "The regenerative process of Alzheimer's disease.Proceedings of the XIth International Congress of Neuropathology." Neuropathology. 4. 110-115 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ivy Go et al.: "The protease inhibitor leupeptin induces several signs of aging in brain,retina and internal organs of young rats." Arch Gerontol Geriat. 12. 119-131 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tokuda T et al.: "Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta protein and tau protein." Acta Neuropathol. 82. 280-285 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizutani T et al.: "Clinicopathologic study of dementia in Parkinson disease." Dementia. 2. 229-236 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Watanabe N et al.: "Tau 2:A probe for a Ser-conformation in the amino terminus of τ." J Neurochem. 58. 960-966 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kanemaru K et al.: "Fetal-type phosphorylation of the tau in paired helical filaments." J Neurochem. 58. 1667-1675 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Choi-Miura NH et al.: "SP40,40 is a constituent of Alzheimer's amyloid." Acta Neuropathol. 83. 260-264 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Iwatsubo T et al.: "Lack of ubiquitin immunoreactivities at both ends of neuropil threads -possible bidirectional growth of neuropil threads-." Am J Pathol. 140. 277-282 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hasegawa M et al.: "Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease" J Biol Chem. 267. 17047-17054 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F et al.: "A novel correlation between the levels of β-amyloid protein precursor and tau transcripts in the aged human brain." J Neurochem. 59. 1117-1125 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yanagisawa K et al.: "Secretory pathway of β/A4 amyloid protein precursor in familial Alzheimer's disease with Val_<717> to Ile mutation." Neurosci Lett. 144. 43-45 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuji S et al.: "Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease." EMBO J. 11. 4843-4850 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F et al.: "β-Amyloid protein precursor and tau mRNA levels versus β-amyloid plaque and neurofibrillary tangles in the aged human brain." J Neurochem. 60. 1658-1664 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hasegawa M et al.: "Characterization of two distinct monoclonal antibodies to paired helical filaments(PHF)-Further evidence for fetal-type phosphorylation of the tau in PHF-." J Neurochem. 60. 2068-2077 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morishima M et al.: "Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments." Neuron. 10. 1151-1160 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshida H et al.: "tau in paired helical filaments(PHF) is functionally distinct from fetal tau.-assembly incompetence of PHF-tau-." J Neurochem. 61. 1183-1186 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kobayashi H et al.: "Molecular cloning of rat growth inhibitory factor cDNA and the expression in the central nervous system." Mol Brain Res. 19. 188-194 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Watanabe A et al.: "In vivo phosphorylation sites in fetal and adult rat tau." J Biol Chem. 268. 25712-25717 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueda K et al.: "Molecular cloning of a novel component of amyloid in Alzheimer's disease." Proc Natl Acad Sci USA. 90. 11282-11286 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F et al.: "Down's syndrome:Upregulation of β-amyloid protien precursor and tau mRNAs and their defective coordinatioin." J Neurochem. 62. 1062-1066 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori H et al.: "Brain Pathology" Neurofibrillary tangles,dystrophic neurites (curly fibers),and abnormal phosphorylation of tau., 5 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuzuhara S et al.: "Frontiers of Alzheimer Research" β-protein and tau immunohistochemistry on brains of normal aging and dementia., 11 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H et al.: "Frontiers of Alzheimer Research" Localization of amyloid β/A4 protein precursor in the Alzheimer brains., 8 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H, Ishiguro K, Shoji M, Yamazaki T, Nakazato Y, Ihara Y, Hirai S: "Amyloid beta/A4 protein precursor is bound to neurofibrillary tangles in Alzheimer-type dementia." Brain Res. 537. 318-322 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H, Nakazato Y, Shoji M, Okamoto K, Ihara Y, Morimatu M, Hirai S: "Secondary deposition of beta amiloid within extracellular neurofibrillary tangles in Alzheimer-type dementia." Am J Pathol. 138. 699-705 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H, Nakazato Y, Kawarabayashi T, Ishiguro K, Ihara Y, Morimatsu H, Hirai S: "Extracellular neurofibrillary tangles associated with degenerating neurites and neuropil threads in Alzheimer-type dementia." Acta Neuropathol. 81. 603-609 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F, Shimada H, Oyama R, Titani K, Ihara Y: "Differential expression of beta amyloid protein precursor (APP) and tau mRNA in the aged human brain : Individual variability and correlation between APP-751 and four-repeat tau." J Neuropathol Exp Neurol. 50. 560-578 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morishima-Kawashima M, Arai T, Ogawara M, Takio K, Titani K, Saitoh T, Kosik KS, Ihara Y: "A possible fetal antigen of M_r 70,000 in neurofibrillary tangles." Brain Res. 554. 316-320 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchida Y, Takio K, Titani K, Ihara Y, Tomonaga M: "The growthinhibitory factor that is deficient in the Alzheimer's disease brain is a 68-amino acid metallothionein-like protein." Neuron. 7. 337-347 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ihara Y, Hasegawa M, Miura R, Kanemaru K, Uchida Y, Takio K, Titani K: "The regenerative process of Alzheimer's disease. Proceedings of the XIth International Congress of Neuropathology." Neuropathol. (Suppl 4). 110-115 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ivy GO, Ihara Y, Kitani K: "The protease inhibitor leupeptin induces several signs of aging in brain, retina and internal organs of young rats." Arch Gerontol Geriat. 12. 119-131 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizutani T, Aki M, Shiozawa R, Tanabe H, Uchigata M, Oda M, Endo Y, Hara K, Ihara Y: "Clinicopathologic study of dementia in Parkinson disease." Dementia. 2. 229-236 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tokuda T, Ikeda S, Yanagisawa N, Ihara Y, Glenner GG: "Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta protein and tau protein." Acta Neuropathol. 82. 280-285 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Watanabe N, Takio K, Hasegawa M, Arai T, Titani K, Ihara Y: "Tau 2 A probe for a Ser-conformation in the amino terminus of gamma." J Neurochem. 58. 960-966 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kanemaru K, Takio K, Miura R, Titani K, Ihara Y: "Fetal-type phosphorylation of the tau in paired helical filaments." J Neurochem. 58. 1667-1675 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Choi-Miura NH, Ihara Y, Fukuchi K, Takeda M, Nakano Y, Tobe T, Tomita M: "SP40, 40 is a constituent of Alzheimer's amyloid." Acta Neuropathol. 83. 260-264 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Iwatsubo T, Hasegawa M, Esaki Y, Ihara Y: "Lack of ubiquitin immunoreactivities at both ends of neuropil threads - possible bidirectional growth of neuropil threads -." Am J Pathol. 140. 277-282 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hasegawa M, Morishima-Kawashima M, Takio K, Suzuki M, Titani K, Ihara Y: "Protein sequence and mass spectrometric analyzes of tau in the Alzheimer's disease brain." J Biol Chem. 267. 17047-17054 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F, Shimada H, Oyama R, Titani K, Ihara Y: "A novel correlation between the levels of beta-amyloid protein precursor and tau transcripts in the aged human brain." J Neurochem. 59. 1117-1125 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F, Shimada H, Oyama R, Titani K, Ihara Y: "beta-Amyloid protein precursor and tau mRNA levels versus beta-amyloid plaque and neurofibrillary tangles in the aged human brain." J Neurochem. 60. 1658-1664 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hasegawa M, Watanabe A, Takio K, Suzuki M, Arai T, Titani K, Ihara Y: "Characterization of two distinct monoclonal antibodies to paired helical filaments (PHF) - Further evidence for fetal-type phosphorylation of the tau in PHF -." J Neurochem. 60. 2068-2077 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yanagisawa K, Ihara Y, Miyatake T: "Secretory pathway of beta/A4 amyloid protein precursor in familial Alzheimer's disease with Val_<717> to Ile mutation." Neurosci Lett. 144. 43-45 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuji S, Kobayashi H, Uchida Y, Ihara Y, Miyatake T: "Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease." EMBO J. 11. 4843-4850 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshida H, Ihara Y: "gamma in paired helical filaments is functionally distinct from fetal tau. - assembly incompetence of paired helical filament-gamma -." J Neurochem. 61. 1183-1186 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Titani K, Ihara Y: "Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments." Neuron. 10. 1151-1160 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kobayashi H, Uchida Y, Ihara Y, Nakajima K, Kohsaka S, Miyatake T, Tsuji S: "Molecular cloning of rat growth inhibitory factor cDNA and the expression in the central nervous system." Mol Brain Res. 19. 188-194 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Watanabe A, Hasegawa M, Suzuki M, Takio K, Morishima-Kawashima M, Titani K, Arai T, Kosik KS, Ihara Y: "In vivo phosphorylation sites in fetal and adult rat tau." J Biol Chem. 268. 25712-25717 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DAC, Kondo J, Ihara Y, Saitoh T: "Molecular cloning of a novel component of amyloid in Alzheimer's disease." Proc Natl Acad Sci USA. 90. 11282-11286 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Oyama F, Cairns NJ, Shimada H, Oyama R, Titani K, Ihara Y: "Down's syndrome : Upregulation of beta-amyloid protein precursor and tau mRNAs and their defective coordination." J Neurochem. 62. 1062-1066 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori H, Ihara Y: Neurofibrillary tangles, dystrophic neurites (curly fibers), and abnormal phosphorylation of tau.Brain Pathology, 273-277 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuzuhara S, Ihara Y, Shimada H, Toyokura Y: beta-protein and tau immunohistochemistry on brains of normal aging and dementia.Frontiers of Alzheimer Research (eds Ishii T,Allsop D,selkoe DJ), Elsevier, Amsterdam, 87-97 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H, Shoji M, Kawarabayashi T, Yamazaki T, Nakazato Y, Hirai S, Ihara Y: Localization of amyloid beta/A4 protein precursor in the Alzheimer brains.Frontiers of Alzheimer Research (eds Ishii T,Selkoe DJ,Allsop D), Elsevier Science Publishers B.V., Amsterdam, 155-162 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamaguchi H et al.: "Amyloid β/A4 protein precursor is bound to neurofibrillary tangles in Alzheimer-type dementia." Brain Res. 537. 318-322 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamaguchi H et al.: "Secondary deposition of β amyloid within extracellular neurofibrillary tangles in Alzheimer-type dementia." Am.J.Pathol.138. 699-705 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamaguchi H et al.: "Extracellular neurofibrillary tangles associated with de generating neurites and neuropil threads inAlzheimer-type dementia." Acta Neuropathol.81. 603-609 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Oyama F et al.: "Differential expression of β amyloid protein precursor(APP)and tau mRNA in the aged human brain:Individual variability and correlation between APP-751 and four-repeat tau." J.Neuropathol.Exp.Neurol.50. 560-578 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morishima M et al.: "A possible fetal antigen of Mr 70,000 in neurofibrillary tangles." Brain Res.554. 316-320 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uchida Y et al.: "The growth in-hibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein like protein." Neuron. 7. 337-347 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ihara Y et al.: "The regenerative process of Alzheimer's disease.Proceedings of the XIth International Congress of Neuropathology." Neuropathology. 4. 110-115 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ivy Go et al.: "The protease inhibitor leupeptin induces several signs of aging in brain,retina and internal organs of young rats." Arch Gerontol Geriat. 12. 119-131 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tokuda T et al.: "Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta protein and tau protein." Acta Neuropathol. 82. 280-285 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mizutani T et al.: "Clinicopathologic study of dementia in Parkinson disease." Dementia. 2. 229-236 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Watanabe N et al.: "Tau 2:A probe for a Ser-conformation in the amino terminus of τ." J Neurochem. 58. 960-966 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kanemaru K et al.: "Fetal-type phosphorylation of the tau in paired helical filaments." J Neurochem. 58. 1667-1675 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Choi-Miura NH et al.: "SP40,40 is a constituent of Alzheimer's amyloid." Acta Neuropathol. 83. 260-264 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwatsubo T et al.: "Lack of ubiquitin immunoreactivities at both ends of neuropil threads-possible bidirectional growth of neuropil threads-." Am J Pathol. 140. 277-282 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hasegawa M et al.: "Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease" J Biol Chem. 267. 17047-17054 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Oyama F et al.: "A novel correlation between the levels of β-amyloid protein precursor and tau transcripts in the aged human brain." J Neurochem. 59. 1117-1125 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yanagisawa K et al.: "Secretory pathway of β/A4 amyloid protein precursor in familial Alzheimer's disease with Val_<717> to Ile mutation." Neurosci Lett. 144. 43-45 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsuji S et al.: "Molecular cloning ofhuman growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease." EMBO J. 11. 4843-4850 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Oyama F et al.: "β-Amyloid protein precursor and tau mRNA levels versus β-amyloid plaque and neurofibrillary tangles in the aged human brain." J Neurochem. 60. 1658-1664 (1993)

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      1993 Annual Research Report
  • [Publications] Hasegawa M et al.: "Characterization of two distinct monoclonal antibodies to paired helical filaments(PHF)-Further evidence for fetal-type phosphorylation of the tau in PHF-." J Neurochem. 60. 2068-2077 (1993)

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      1993 Annual Research Report
  • [Publications] Morishima M et al.: "Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments." Neuron. 10. 1151-1160 (1993)

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      1993 Annual Research Report
  • [Publications] Yoshida H et al.: "tau in paired helical filaments(PHF)is functionally distinct from fetal tau.-assembly incompetence of PHF-tau-." J Neurochem. 61. 1183-1186 (1993)

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      1993 Annual Research Report
  • [Publications] Kobayashi H et al.: "Molecular cloning of rat growth inhibitory factor cDNA and the expression in the central nervous system." Mol Brain Res. 19. 188-194 (1993)

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      1993 Annual Research Report
  • [Publications] Watanabe A et al.: "In vivo phosphorylation sites in fetal and adult rat tau." J Biol Chem. 268. 25712-25717 (1993)

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      1993 Annual Research Report
  • [Publications] Ueda K et al.: "Molecular cloning of a novel component of amyloid in Alzheimer's disease." Proc Natl Acad Sci USA. 90. 11282-11286 (1993)

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      1993 Annual Research Report
  • [Publications] Oyama F et al: "Down's syndrome:Upregulation of β- amyloid protien precursor and tau mRNAs and their defective coordinatioin." J Neurochem. (in press).

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      1993 Annual Research Report
  • [Publications] Iwatsubo T et al.: "Lack of ubiquitin immunoreactivities at both ends of neuropil threads -- possible bidirectional growth of neuropil threads--." American Journal of Pathology. 140. 277-282 (1992)

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      1992 Annual Research Report
  • [Publications] Hasegawa M et al.: "Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain." Journal of Biological Chemistry. 267. 17047-17054 (1992)

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      1992 Annual Research Report
  • [Publications] Oyama F et al.: "A novel correlation between the levels of beta amyloid protein precursor and tau transcripts in the aged brain." Journal of Neurochemistry. 59. 1117-1125 (1992)

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      1992 Annual Research Report
  • [Publications] Tsuji S et al.: "Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease." EMBO journal. 11. 4843-4850 (1992)

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      1992 Annual Research Report
  • [Publications] Oyama F et al.: "beta Amyloid protein precursor and tau mRNA levels versus beta amyloid plaque and neurofibrillary tangles in the aged human brain." Journal of Neurochemistry. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hasegawa M et al: "Characterization of two distinct monoclonal antibodies to paired helical filaments (PHF)--Further evidence for fetal-type phosphorylation of the tau in PHF" Journal of Neurochemistry. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Oyama F.: "Differential expression of B amyloid protein precursor (APP) and tau mRNA in the agged human brain:Individual variablity and correlation between APP-751 and fourrepeat tau" J Neuropathol Exp Neurol. 50. 560-578 (1991)

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      1991 Annual Research Report
  • [Publications] Morishima M.: "A possible fetal antigen of Mr 70,000 in neurofibrillary tangles" Brain Res. 554. 316-320 (1991)

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      1991 Annual Research Report
  • [Publications] Uchida Y.: "The growth-inhibitory factor that is deficient in the Alzheimer's disease brain is a 68-amino acid metallothionein-like protein" Neuron. 7. 337-347 (1991)

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      1991 Annual Research Report
  • [Publications] Iwatsubo T.: "Lack of ubiquitin immunoreactivities at both ends of neuropil threads-possible bidirectional growth of neuropil threads ---" AM J Pathol. 140. 277-282 (1992)

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      1991 Annual Research Report
  • [Publications] Watanabe N.: "Tau 2 A probe for a Ser-conformation in the amino terminus of tau" J Neurochem.

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      1991 Annual Research Report
  • [Publications] Kanamaru K.: "Fetal-type phosphorylation of the tau in paired helical filaments" J Neurochem.

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      1991 Annual Research Report
  • [Publications] Ihara Y.: "Aging of the Brain:Cellular and Molecular Aspects of Brain Aging and Alzheimer's Disease" Kargar,Tokyo, 6 (1990)

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      1991 Annual Research Report
  • [Publications] Mori H.: "Brain Pathology" International Society of Neuropathology, 5 (1991)

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      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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