1999 Fiscal Year Final Research Report Summary
Study of pathogenesis of Abeta amyloid deposits in Alzheimer's disease
| Project/Area Number |
10832003
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
老化(加齢)
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| Research Institution | Gunma University |
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Principal Investigator |
SHOJI Mikio School of Medicine, Gunma University Lecturer, 医学部, 講師 (60171021)
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| Co-Investigator(Kenkyū-buntansha) |
HARIGAYA Yasuo School of Medicine, Gunma University Lecturer, 医学部, 講師 (90165035)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Alzheimer's disease / Amyloid / Abeta 42 |
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| 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.
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Research Products
(27 results)
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[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
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[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
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[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
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[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
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[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
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[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
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[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
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[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
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[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
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