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Study of pathogenesis of Abeta amyloid deposits in Alzheimer's disease

Research Project

Project/Area Number 10832003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 老化(加齢)
Research InstitutionGunma University

Principal Investigator

SHOJI Mikio  School of Medicine, Gunma University Lecturer, 医学部, 講師 (60171021)

Co-Investigator(Kenkyū-buntansha) HARIGAYA Yasuo  School of Medicine, Gunma University Lecturer, 医学部, 講師 (90165035)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsAlzheimer's disease / Amyloid / Abeta 42 / Aβ40 / リポ蛋白結合型 / リポ蛋白非結合型 / 血液Aβ / Aβ / 脳Aβ / 脳脊髄液Aβ
Research Abstract

To clarify the accumulation mechanism of physiological peptide, i.e., Abeta amyloid protein (Abeta) in Alzheimer's disease, studies described below were conducted.
1) The levels of Abeta 40/42 of the brain and plasma in transgenic mice (PrP betaAPP751 NL+I, PrP presenilin-1 M146L, PrP presenilin-1 C410Y and APPsw mice) were evaluated showing nmol/g levels Abeta 40/42 were accumulated in the APPsw brain and fmol and pmol level increase of Abeta 40/42 were observed in the brain and plasma in all transgenic mice line.
2) The age-related physiological alteration of Abeta 40/42 in CSF and plasma were observed in normal control subjects.
3) The clinical usefulness of measurement of CSF tau and Abeta 40/42 is established for a diagnosic marker for AD by large scale multicenter study.
4) The effect of apoE4 on advance of dementia and CSF tau concentrations were revealed.
5) The amounts of Abeta 40/42 accumulation in the AD brain were nmol/g levels, but any Abeta accumulation was observed in control brains. Abeta 40 was detected in normal human urine.
6) Plasma lipoprotein unbinding Abeta 40/42 was increased in sporadic AD and Down syndrome patients showing the levels of lipoprotein free Abeta40/42 as the possible diagnostic marker for AD and the important role of plasma lipoprotein for sequestration Abeta40/42.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Matsubara E.,Shoji M.et al.: "Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer's disease and Down's syndrome"Annals of Neurology. 45. 537-541 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanidokoro Y.,Shoji M.et al.: "Carbonyl-terminal fraquents of presenilin-1 are closey related to cytoskeletal abnormalities in Alzheimer's brains"Biochem. Biophys. Res. Commun.. 256. 512-518 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hu J.,Shoji M.et al.: "Angiotensin-Converting enzyme g*uotype is associated with Alzheimer disease in the Japanese population"Neurosci. Lett.. 277. 65-67 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kanai M.,Shoji M.et al.: "Apolipoprotein E4 accelerates dementia and increases cerebrospinal tau levels in Alzheimer's disease"Neurosci. Lett.. 267. 65-68 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urakami K.,Shoji M.et al.: "A comparison of tau protein in cerebrospinal fluid between corticohusal degeneration and progressive supranuclear palsy"Neurosci. Lett.. 259. 127-129 (199)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda Y.,Shoji M.et al.: "Molecular and clinical analysis of spirocerebellar ataxia type8 in Japan"Neurology. 54. 950-955 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 東海林幹夫: "老年期痴呆診療マニュアル(第2版)"日本医師会/南江堂. 341 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 東海林幹夫: "アルツハイマー病の新しい展開"羊土社. 170 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji M, Kawarabayashi T, Sato M, Sasaki A, Saido TC, Matsubara E, Tomidokoro Y, Kanai M, Shizuka M, Ushiguro K, Ikeda M, Harigaya Y, Okamoto K, Hirai S.: "Age-related amyloid b protein accumulation induces cellular death and macrophage activation in transgenic mice."J Pathol. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji M, Harigaya Y, Sasaki A, Ishiguro K, Matsubara E, Watanabe M, Ikeda M, Kanai M, Tomidokoro Y, Shizuka M, Amari M, Kosaka K, Nakazato Y, Okamoto K, Shunsaku Hirai S.: "Accumulation of NACP/α-synuclein in Lewy body disease and multiple system atrophy."J Neurol Neurosurg Psychiatry. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji M, Kawarabayashi T, Matsubara E, Ikeda M, Ishiguro K, Harigaya Y, Okamoto K.: "The distribution of the amyloid b protein precursor in the Alzheimer's disease brain."Psychiat Clin Neurosci. 54. 45-54 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda Y, Shizuka M, Watanabe M, Okamoto K, Shoji M,: "Molecular and clinical analysis of spinocerebellar ataxia type 8 in Japan."Neurology. 54. 950-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsubara E, Ghiso J, Frangione B, Amari M, Tomidokoro Y, Ikeda Y, Harigaya Y, Okamoto K, Shoji M,: "Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer's disease and Down's syndrome."Ann Neurol. 45. 537-41 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomidokoro Y, Ishiguro K, Igeta Y, Matsubara E, Kanai M, Shizuka M, Kawarabayashi T, Harigaya Y, Kawakatsu S, Ii K, Ikeda M, St George-Hyslop PH, Hirai S, Okamoto K, Shoji M,: "Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal abnormalities in Alzheimer's brains."Biochem Biophys Res Commun. 256. 512-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hu J, Miyatake F, Aizu Y, Nakagawa H, Nakamura S, Tamaoka A, Takahashi R, Urakami K, Shoji M,: "Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population."Neurosci Lett. 277. 65-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shizuka M, Ikeda Y, Watanabe M, Okamoto K, Shoji M, Ikegami T, Hayasaka K.: "A novel mutation of the myelin P(o) gene segregating Charcot-Marie-Tooth disease type 1B manifesting as trigeminal nerve thickening."J Neurol Neurosurg Psychiatry. 67. 250-1 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kanai M, Shizuka M, Urakami K, Matsubara E, Harigaya Y, Okamoto K, Shoji M,: "Apolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease."Neurosci Lett. 267. 65-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urakami K, Mori M, Wada K, Kowa H, Takeshima T, Arai H, Sasaki H, Kanai M, Shoji M, Ikemoto K, Morimatsu M, Hikasa C, Nakashima K.: "A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy."Neurosci Lett. 259. 127-9 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Watanabe M, Sugai Y, Concannon P, Koenig M, Schmitt M, Sato M, Shizuka M, Mizushima K, Ikeda Y, Tomidokoro Y, Okamoto K, Shoji M,: "Familial spinocerebellar ataxia with cerebellar atrophy, peripheral neuropathy, and elevated level of serum creatine kinase, gamma-globulin, and alpha-fetoprotein."Ann Neurol. 44. 265-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kanai M, Matsubara E, Isoe K, Urakami K, Nakashima K, Arai H, Sasaki H, Abe K, Iwatsubo T, Kosaka T, Watanabe M, Tomodokoro Y, Shizuka M, Mizushima K, Nakamura T, Igeta Y, Ikeda Y, Amari M, Kawarabayashi T, Ishiguro K, Harigaya Y, Wakabayashi K, Okamoto K, Hirai S, Shoji M,: "Longitudinal study of cerebrospinal fluid levels of tau, Aβ 1-40, and Aβ 1-42(43) in Alzheimer's disease : a study in Japan."Ann Neurol. 44. 17-26 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kano S, Watanabe M, Kanai M, Koike R, Onodera O, Tsuji S, Okamoto K, Shoji M.: "A Japanese family with adrenoleukodystrophy with a codon 291 deletion : a clinical, biochemical, pathological, and genetic report."J Neurol Sci. 158. 187-92 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji M, Matsubara E, Kanai M, Watanabe M, Nakamura T, Tomidokoro Y, Shizuka M, Wakabayashi K, Igeta Y, Ikeda Y, Mizushima K, Amari M, Ishiguro K, Kawarabayashi T, Harigaya Y, Okamoto K, Hirai S.: "Combination assay of CSF tau, A beta 1-40 and A beta 1-42(43) as a biochemical marker of Alzheimer's disease."J Neurol Sci. 158. 134-40 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isoe K, Urakami K, Shoji M, Nakashima K.: "Intracranial calcification with IgG lambda M-proteinaemia : a case report."J Neurol Neurosurg Psychiatry. 64. 561-3 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji M, Kawarabayashi T, Sato M, Sasaki A, Matsubara E, Igeta Y, Kanai M, Tomidokoro Y, Shizuka M, Ishiguro K, Harigaya Y, Okamoto K, Hirai S.: "Accumulation of amyloid beta protein in transgenic mice."Neurobiol Aging. 19. S59-63 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji M, Harigaya Y.: "Biochemical heterogeneity of Alzheimer's disease."Neuropathology. 18. 116-120 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura T, Shoji M, et al.: "Basic and clinical studies on the measurement of tau protein in cerebrospinal fluid as a biological marker for Alzheimer's disease and related disorders : multicenter study in Japan."Methods Find Exp Clin Pharmacol. 20. 227-235 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura T, Shoji M, et al.: "Basic and clinical studies on ApoE gene typing by line probe assay (LiPA) as a biological marker for Alzheimer's disease and related disorders : multicenter study in Japan."Methods Find Exp Clin Pharmacol. 20. 793-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsubara E,Shouji M,et al: "Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer's disease and Down's syndrome"Annals of Neurology. 45. 537-541 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomidokoro Y,Shouji M,et al: "Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal abnormalities in Alzheimer's brains"Biochem Biophys Res Commun. 256. 512-518 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hu J,Shouji M et al: "Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population"Neurosci Lett.. 277. 65-67 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kanai M,Shouji M,et al: "Apolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease"Neurosci Lett.. 267. 65-68 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Urakami K,Shouji M et al: "A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy"Neurosci Lett.. 259. 127-129 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda Y,Shouji M et al: "Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan"Neurology. 54. 950-955 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 東海林幹夫: "老年期痴呆診療マニュアル(第∂版)"日本医師会/南江堂. 341 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 東海林幹夫: "アルツハイマー病の新しい展開"羊土社. 170 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shoji M,Harigaya Y et al.: "Combination assay of CSF tau,Aβ_<1-40> and Aβ_<1-42(43)> as a biochemical marker of Alzheimer's disease." J Neurol Sci. 158. 134-140 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoji M,Harigaya Y: "Biochemical heterogeneity of Alzheimer's disease" Neuropathology. 18. 116-120 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoji M,Harigaya Y et al.: "Accumulation of amyloid β protein transgenic mice." Neurobiol Aging. 19. S59-63 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsubara E,Shoji M,Harigaya Y.: "Lipoprotein-free amyloidogenic peptides in plasma are elevated in the patients with sporadic Alzheimer's diseace and Down's syndrome" Ann Neurol. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomidokoro Y.Harigaya Y.Shoji: "Carboxylterminal fragments' of presenilin-lare closely relatea Metal to cytoskeletal abnormality in Alzheimer's brains." Biochem Biophys Res Commun. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanai M,Harigaya Y,Shoji M,et al.: "Longitudinal study of cerebrospinal fluid levels of Tau,Aβ_<1-40> and Aβ_<1-42(43)> in Alzheimer's dicease:A Study in Japan" Ann Neurol. 44. 17-26 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林幹夫: "アルツハイマー病の病理と成因.平井俊策編.老化の仕組みと疾患" 羊土社, 7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林幹夫: "アルツハイマー病の動物モデル-解明点と問題点.井原康夫編 新臨床医のための分子医学シリーズ" 羊土社, (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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