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アルツハイマー病脳アミロイドイメージングの分子論的解明

Research Project

Project/Area Number 20023027
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka City University

Principal Investigator

森 啓  Osaka City University, 大学院・医学研究科, 教授 (10159189)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2009: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2008: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywordsアルツハイマー病 / アミロイド / PIB / 画像診断 / モデルマウス / アルツハイマー / イメージング / 老人班 / 家族性
Research Abstract

本研究は、高齢化社会での重要な医学的、社会的問題となっているアルツハイマー病認知症に関する研究であり、主として正確な診断法に関する検討を実施したものである。具体的には、臨床症例を対象とした脳画像法であるPiB-PETの意義を分析するものであり、基本的には健常人と孤発性アルツハイマー病患者間の比較検討を中心とした解析である。とくに早期発症型家族性アルツハイマー病を対象とした脳画像を取り上げることで、早期脳画像変化に焦点を絞ることを目的とした。さらに臨床的認知症度とPiBシグナルに基づく脳内アミロイド蓄積量との関係についえも調査した。PiBシグナルとFDG-PETシグナルを比較検討することで、脳機能とアミロイド蓄積量との関係も重要な課題であり、詳細な検討を実施した。現在世界的に試用されている化合物として米国ピッツバーグ大学で開発されたPiB化合物がある。このPiB-PETシグナルが意味する画像解析は未完成であることから、多様な臨床症例にて分析が進んでいる。本研究においては、正常例、孤発性アルツハイマー病症例をベースに、家族性アルツハイマー病を対象とした本PiB-PET研究を中心に実施した。概ね従来研究成果を支持する結果であり矛盾しないことを確認することで、本研究組織・体制に間違いがないことが確認された。さらに詳細には、家族性アルツハイマー病の特徴として、線状体での高いPiB保持率に対して皮質ではやや低いPiB保持率であることが明らかとなった。しかも、臨床症状での多様性とは異なり、PiBによる検討では脳内Aβ蓄積のパターンと程度は、各変異種によらないと結論した。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (28 results)

All 2010 2009 2008 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (18 results) Remarks (1 results)

  • [Journal Article] DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning.2010

    • Author(s)
      Nagata T, Tomi y a m a T, Mori H, Yaguchi T, Nishizaki T
    • Journal Title

      Behavioural brain research 206

      Pages: 151-4

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A mouse model of amyloid b oligomers : Their contribution to synapticalteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo"2010

    • Author(s)
      Tomiyama T, Matsuyama S, Iso H, Umeda T, Takuma T, Ohnishi K, Ishibashi K, Teraoka R, Sakama N, Yamashita T, Nishitsuji K, ItoK, Shimada H, Mary Lambert, William Klein, Mori H
    • Journal Title

      Journal of Neuroscience (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oligomeric amyloid beta-protein as a therapeutic target in Alzheimer's disease : its significance based on its distinct localization and the occurrence of a familial variant form.2009

    • Author(s)
      Ito K, Ishibashi K, Tomiyama T, Umeda T, Yamamoto K, Kitajima E, Idomoto T, Nagatomo T, Mori H
    • Journal Title

      Current Alzheimer research 6

      Pages: 132-6

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The E693Delta mutation in amyloid precursor protein increases intracellular accumulation of amyloid beta oligomers and causes endoplasmic reticulum stress-induced apoptosis in cultured cells.2009

    • Author(s)
      Nishitsuji K, Tomiyama T, Ishibashi K, Ito K, Teraoka R, Lambert MP, Klein WL, Mori H
    • Journal Title

      The American journal of pathology 174

      Pages: 957-69

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types.2009

    • Author(s)
      Villemagne VL, Ataka S, Mizuno T, Brooks WS, Wada Y, Kondo M, Jones G, Watanabe Y, Mulligan R, Nakagawa M, Miki T, Shimada H, O'Keefe GJ, Masters CL, Mori H, Rowe CC
    • Journal Title

      Archives of neurology 66

      Pages: 1537-44

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amyloid-β E22D variant induces synaptic alteration in mouse hippocampal slices2009

    • Author(s)
      Hiroshi Takuma, et.al.
    • Journal Title

      NeuroReport 19

      Pages: 615-619

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oligomeric Amyloid β-Protein as a Therapeutic Target in Alzheimer's Disease : Its Significance Based on its Distinct Localization and the Occurrence of a Familial Variant Form2009

    • Author(s)
      Kazuhiro Ito, et.al.
    • Journal Title

      Current Alzheimer Research 6

      Pages: 132-136

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The E693delta Mutation in Amyloid Precursor Protein Increases Intracellular Accumulation of Amyloid beta oligomers and Causes Endoplasmic Reticulum Stress-Induced Apoptosis in Cultured Cells2009

    • Author(s)
      Kazuchika Nishitsuji, et.al.
    • Journal Title

      Am. J. Pathol 174

      Pages: 957-969

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new amyloid β variant favoring oligomerization in Alzheimer-type dementia2008

    • Author(s)
      Takami Tomiyama, et.al.
    • Journal Title

      Ann. Neurol 63

      Pages: 377-387

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] アルツハイマー病はアミロイドが原因でおこる2009

    • Author(s)
      森啓
    • Organizer
      日本女性薬剤師会
    • Place of Presentation
      星薬科大学メインホール
    • Year and Date
      2009-06-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] Beyond amyloid b fibrils.2009

    • Author(s)
      Mori H.
    • Organizer
      Wenner-Gren Foundations International Symposium "Alzheimer therapy : still a challenge"
    • Place of Presentation
      Wenner-Gren Center, Stockholm
    • Related Report
      2009 Annual Research Report
  • [Presentation] 老人斑を越えて2009

    • Author(s)
      森啓
    • Organizer
      第24回日本老年精神医学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Homozygous APP mutations and Alzheimer's disease2009

    • Author(s)
      Mori H.
    • Organizer
      12th International Conference on Alzheimer's Disease (ICAD)
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2009 Annual Research Report
  • [Presentation] A transgenic mouse model of amyloid β oligomers : Pathological effects of the E693△ mutation in amyloid precursor protein in vivo.2009

    • Author(s)
      Tomiyama T, Matsuyama S, Iso H, Takuma H, Umeda T, Ohnishi K, Teraoka R, Ishibashi K, Nishitsuji K, Ito K, Borchelt D.R, Lambert M.P, Klein W.L, Mori H.
    • Organizer
      12th International Conference on Alzheimer's Disease (ICAD)
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2009 Annual Research Report
  • [Presentation] A transgenic mouse model of amyloid β oligomers.2009

    • Author(s)
      富山貴美、松山正剛、磯博行、梅田知宙、詫間浩、大西紀陽久、石橋謙一、寺岡理恵、坂間直美、西辻和親、伊藤和博、David R.Borchelt, Mary P.Lambert, William L.Klein, 森啓
    • Organizer
      第28回日本認知症学会学術集会
    • Place of Presentation
      東北大学百周年記念会館・艮陵会館
    • Related Report
      2009 Annual Research Report
  • [Presentation] Regulation of cholesterol efflux by amyloid b secretion(Ab分泌によるコレステロールeffluxの制御)2009

    • Author(s)
      梅田知宙, 森啓, Hui Zheng, 富山貴美, et al
    • Organizer
      第28回日本認知症学会学術集会
    • Place of Presentation
      東北大学百周年記念会館・艮陵会館
    • Related Report
      2009 Annual Research Report
  • [Presentation] 高齢ホッキョクグマの脳神経病理学的剖検報告2009

    • Author(s)
      藤田有紀、岡橋要、梅田知宙、山本圭一、森啓
    • Organizer
      第28回日本認知症学会学術集会.
    • Place of Presentation
      東北大学百周年記念会館・艮陵会館
    • Related Report
      2009 Annual Research Report
  • [Presentation] The International Symposium on Early Detection and Rehabilitation Technology of Dementia2009

    • Author(s)
      Mori,H.
    • Organizer
      Ab monomer, oligomer and fibril in Alzheimer's disease
    • Place of Presentation
      Okayama Univ.
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification and characterization of a novel APP mutation (E693Δ) in familial Alzheimer's disease2008

    • Author(s)
      Takami Tomiyama, et.al.
    • Organizer
      The llth International conference on Alzheimer's disease
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2008-07-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] Amyloid imaging of a patient with Alzheimer's disease harboring anovel APP mutation (E6934)2008

    • Author(s)
      Hiroyuki Shimada, et.al.
    • Organizer
      The 11^<th> International conference on Alzheimer's disease
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2008-07-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] Synaptic toxicity of an Aβ variant in Alzheimer-type dementia2008

    • Author(s)
      森啓, et.al.
    • Organizer
      第31回日本神経科学会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2008 Annual Research Report
  • [Presentation] Pattern of Ab deposition in Familial Alzheimer's disease is irrespective of mutation type or cognitive status2008

    • Author(s)
      Victor L. Villemagne, et.al.
    • Organizer
      The 56^<th> SNM Annual Meeting
    • Place of Presentation
      New Orleans, LA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Frontotemporal Dementia increase the risk of nursing home placement?2008

    • Author(s)
      Aki nakanishi, et.al.
    • Organizer
      The 6th International Conference on Frontotemporal Dementias
    • Place of Presentation
      Rotterdam, The Netherlands
    • Related Report
      2008 Annual Research Report
  • [Presentation] Aβのオリゴマー化を促進するAPP変異E693Δの同定2008

    • Author(s)
      富山貴美, et.al.
    • Organizer
      27回日本認知症学会
    • Place of Presentation
      前橋テルサ
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規APP変異(E693Δ)を示した認知症患者における臨床像2008

    • Author(s)
      嶋田祐之, et.al.
    • Organizer
      27回日本認知症学会
    • Place of Presentation
      前橋テルサ
    • Related Report
      2008 Annual Research Report
  • [Presentation] A novel function of amyloid β in cholesterol homeostasis2008

    • Author(s)
      梅田知宙, et.al.
    • Organizer
      27回日本認知症学会
    • Place of Presentation
      前橋テルサ
    • Related Report
      2008 Annual Research Report
  • [Presentation] The E693A mutation in amyloid precursor protein increases intracellular accumulation of amyloid β oligomers and causes endoplasmic reticulum stress-induced apoptosis in cultured cells2008

    • Author(s)
      Kazuchika Nishitsuji, et.al.
    • Organizer
      The 38^<th> Annual meeting of the society for neuro science
    • Place of Presentation
      Washington DC
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.osaka-cu.ac.jp/Neurosci

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2018-03-28  

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