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Study for novel biomarkers for Alzheimer's disease

Research Project

Project/Area Number 23659450
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionHirosaki University

Principal Investigator

SHOJI Mikio  弘前大学, 医学(系)研究科(研究院), 教授 (60171021)

Co-Investigator(Renkei-kenkyūsha) MATSUBARA Etsuro  弘前大学, 医学(系)研究科(研究院), 准教授 (70219468)
KAWARABAYASHI Takeshi  弘前大学, 医学部附属病院, 講師 (90186156)
WAKASAYA Yasuhito  弘前大学, 医学部附属病院, 助教 (10598725)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords神経分子病態学 / 神経内科学 / 神経科学 / 臨床神経学 / アルツハイマー病 / バイオマーカー
Research Abstract

To facilitate early diagnosis of AD dementia and other non-AD dementias, simple and quick assay of CSF and plasma biomarkers for Alzheimer disease and non-AD dementia were studied and developed. 1) To identify presence of plasma tau and p-tau, anti-human CNS tau antibodies (tauA/tauB) were developed. Western blot analysis of immunoprecipitated samples from CSF and plasma of TgtauP301L mice using tauA/tauB revealed the real presence of metabolized tau fragments from CNS and PNS. Further confirmation of the presence of CNS tau was necessary. Basic evaluation of CSF and plasma α-synuclein showed adequate reproducibility and sensitivity. Measurements of 105 cases of AD and non-AD dementias showed that increased levels of MCI, and other neurological diseases CSF As40,As42, tauおよび血液As40,As42測定値in AD, MCI, and controls, but, decreased levels of α-synuclein in Parkinson diseases. The levels of CSF As40, As42, tau andplasma As40,As42were correlated with those levels of α-synuclein. High sensitive ELISA of TDP-43 are developing. Candidate 28 molecules as Alzheimer disease identified by proteomics analysis of CSF proteins with more than 30,000 kD were further evaluated using bioinformatics data base for patent filing.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (52 results)

All 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (22 results) (of which Invited: 4 results) Book (16 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians2013

    • Author(s)
      Miyashita A, Koike A, Jun G, Kawarabayashi T, Shoji M,Arai H, Asada T, Harigaya Y, Ikeda M, Amari M, Ikeuchi T, St. George-Hyslop P,
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e58618-e58618

    • DOI

      10.1371/journal.pone.0058618

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sortilin is required for toxic action of Aβ oligomers (AβOs): Extracellular AβOs trigger apoptosis, and intraneuronal AβOs impair degradation pathways2012

    • Author(s)
      Ayumi Takamura
    • Journal Title

      Life Sciences

      Volume: 91 Issue: 23-24 Pages: 1177-1186

    • DOI

      10.1016/j.lfs.2012.04.038

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer's Disease: Clinical Molecular and Genetic Studies on Alzheimer's Disease2012

    • Author(s)
      Shoji M
    • Journal Title

      J Pharmacol Sci

      Volume: (Epub ahead of print)

    • NAID

      10030455602

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Altered Y-secretase activity in mild cognitive impairment and Alzheimer's disease2012

    • Author(s)
      Kakuda N, Shoji M, Arai H, Furukawa K, Ikeuchi T, Akazawa K, Takami M, Hatsuta H, Murayama s, Hashimoto Y, Miyajima M, Arai H, Nagashima Y Yamaguchi H, Kuwano R, Nagaike K, Ihara Y ; the Japanese Alzheimer's Disease Neuroimaging Initiative
    • Journal Title

      Eur J Neurol

      Volume: 4 Issue: 4 Pages: 344-352

    • DOI

      10.1002/emmm.201200214

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cognitive and affective impairments of a novel SCA/MND crossroad mutation Asidan2012

    • Author(s)
      Abe K, et al
    • Journal Title

      Eur J Neurol

      Volume: (Epub ahead of print) Issue: 8 Pages: 1070-1078

    • DOI

      10.1111/j.1468-1331.2012.03669.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] An unusual case of elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple cerebrovascular risk factors.2012

    • Author(s)
      Watanabe M, Adachi Y, Jackson M, Yamamoto-Watanabe Y, Wakasaya Y, Shirahama I, Takamura A, Matsubara E, Kawarabayashi T, Shoji M
    • Journal Title

      J Stroke Cerebrovasc Dis

      Volume: 21(2) Pages: 143-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer's Disease:Clinical Molecular and Genetic Studies on Alzheimer's Disease.2012

    • Author(s)
      Shoji M
    • Journal Title

      J Pharmacol Sci

      Volume: 118(3) Pages: 345-9

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of . Alzheimer's Disease:Clinical Molecular and Genetic Studies on Alzheimer's Disease2012

    • Author(s)
      Shoji M
    • Journal Title

      J Pharmacol Sci

      Volume: 118(3)

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biomarkers of the dementia2011

    • Author(s)
      Shoji M
    • Journal Title

      Int J Alzheimers Dis

      Volume: 2011 Issue: 1 Pages: 564321-564321

    • DOI

      10.4061/2011/564321

    • NAID

      40017342910

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse2011

    • Author(s)
      Takamura A, Okamoto Y, Kawarabayashi T, Yokoseki T, Shibata M, Mouri A, Nabeshima T, Sun H, Abe K, Urisu T, Yamamoto N, Shoji M, Yanagisawa K, Michikawa M, Matsubara E
    • Journal Title

      Mol Neurodegener

      Volume: 6 Issue: 1 Pages: 20-20

    • DOI

      10.1186/1750-1326-6-20

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dissociation of beta-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer' s disease accelerates beta-amyloid-422011

    • Author(s)
      Takamura A, Kawarabayashi T, Yokoseki T, Shibata M, Morishima-Kawashima M, Saito Y, Murayama S, Ihara Y, Abe K, Shoji M, Michikawa M, Matsubara E
    • Journal Title

      assembly. Neurosci Res

      Volume: 89 Issue: 6 Pages: 815-821

    • DOI

      10.1002/jnr.22615

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy.2011

    • Author(s)
      Wakasaya Y, Kawarabayashi T, Watanabe M, Yamamoto-Watanabe Y, Takamura A, Kurata T, Murakami T, Abe K, Yamada K, Wakabayashi K, Sasaki A, Westaway D, Hyslop PS, Matsubara E, Shoji M
    • Journal Title

      J Neurosci Res

      Volume: 89(4) Issue: 4 Pages: 576-84

    • DOI

      10.1002/jnr.22572

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation]2012

    • Author(s)
      東海林幹夫
    • Organizer
      第3回日本血管性認知症研究会シンポジウム「認知症の画像・バイオマーカー」
    • Place of Presentation
      東京ステーションコンファランス
    • Year and Date
      2012-09-08
    • Related Report
      2012 Final Research Report
  • [Presentation] AsOligomerはlipidraftの信号伝達系を障害する2012

    • Author(s)
      瓦林毅,仲田祟,若佐谷保仁,松原悦朗,東海林幹夫
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2012-05-25
    • Related Report
      2012 Final Research Report
  • [Presentation] 動物モデルを用いた脳アミロイドs蛋白の伝播性の検討2012

    • Author(s)
      仲田崇,瓦林毅,若佐谷保仁,松原悦朗,東海林幹夫
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2012-05-25
    • Related Report
      2012 Final Research Report
  • [Presentation] ホットトピックスH(2)-1,アルツハイマー病の新しい診断基準2012

    • Author(s)
      東海林幹夫
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-24
    • Related Report
      2012 Final Research Report
  • [Presentation] リポ蛋白がAs重合化の制御因子である2012

    • Author(s)
      松原悦朗,仲田崇,中畑直子,若佐谷保仁,瓦林毅,東海林幹夫
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2012-05-23
    • Related Report
      2012 Final Research Report
  • [Presentation] アルツハイマー病のバイオマーカー2012

    • Author(s)
      東海林幹夫
    • Organizer
      日本認知症予防医学会,ランチョンセミナー
    • Place of Presentation
      鳥取大学米子キャンパス
    • Year and Date
      2012-04-08
    • Related Report
      2012 Final Research Report
  • [Presentation] アルツハイマー病2012

    • Author(s)
      東海林幹夫
    • Organizer
      第1回認知症研修会in米子
    • Place of Presentation
      ランチョンセミナー
    • Year and Date
      2012-04-07
    • Related Report
      2012 Final Research Report
  • [Presentation] As oligomers in lipid rafts impair signal transduction pathways in transgenic mouse model of Alzheimer's disease2012

    • Author(s)
      Kawarabayashi T, Nakata T, Wakasaya Y, Matsubara E, Shoji M
    • Organizer
      Neuroscience 2012, the Society for Neuroscience, 42th Annual Meeting
    • Place of Presentation
      New Orleans, USA, Oct 13-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Abeta oligomers in lipid rafts impair signal transduction pathways in transgenic mouse model of Alzheimer’s disease2012

    • Author(s)
      Takeshi Kawarabayashi
    • Organizer
      the Society for Neuroscience, 42th Annual Meeting
    • Place of Presentation
      New Orleans
    • Related Report
      2012 Annual Research Report
  • [Presentation] アルツハイマー病:新しい薬物療法の進歩2011

    • Author(s)
      東海林幹夫
    • Organizer
      第29回日本神経治療学会ランチョンセミナー
    • Place of Presentation
      福井フェニックスプラザ
    • Year and Date
      2011-11-18
    • Related Report
      2012 Final Research Report
  • [Presentation] 認知症の画像診断2011

    • Author(s)
      東海林幹夫
    • Organizer
      第27回診療放射線技師総合学術大会ランチョンセミナー
    • Place of Presentation
      青森文化会館
    • Year and Date
      2011-09-18
    • Related Report
      2012 Final Research Report
  • [Presentation] 認知症と薬物療法の進歩2011

    • Author(s)
      東海林幹夫
    • Organizer
      第20回日本意識障害学会,ランチョンセミナー
    • Place of Presentation
      弘前ベストウエスタンホテル
    • Year and Date
      2011-09-03
    • Related Report
      2012 Final Research Report
  • [Presentation] アルツハイマー病と軽度認知障害の発症予測スクリーニングマーカーの検証2011

    • Author(s)
      松原悦朗,高村歩美,若佐谷保仁,瓦林毅,東海林幹夫
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Asoligomerはlipidraftsでtau蓄積を促進する2011

    • Author(s)
      瓦林毅,若佐谷保仁,松原悦朗,東海林幹夫
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
    • Related Report
      2012 Final Research Report
  • [Presentation] DNAmicroarrayによる神経原線維変化の形成および神経細胞死に関与する因子の解析2011

    • Author(s)
      若佐谷保仁,瓦林毅,松原悦朗,東海林幹夫
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
    • Related Report
      2012 Final Research Report
  • [Presentation] アルツハイマー病のバイオマーカー

    • Author(s)
      東海林幹夫
    • Organizer
      日本認知症予防医学会
    • Place of Presentation
      米子
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病の新しい診断基準

    • Author(s)
      東海林幹夫
    • Organizer
      日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病

    • Author(s)
      東海林幹夫
    • Organizer
      認知症研修会in米子
    • Place of Presentation
      米子
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 認知症の画像・バイオマーカー

    • Author(s)
      東海林幹夫
    • Organizer
      日本血管性認知症研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病と軽度認知障害の発症予測スクリーニングマーカーの検証

    • Author(s)
      松原悦朗,高村歩美,若佐谷保仁,瓦林毅,東海林幹夫
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] Abeta oligomerはlipid raftsでtau蓄積を促進する

    • Author(s)
      瓦林毅,若佐谷保仁,松原悦朗,東海林幹夫
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] DNA microarray解析による神経原線維変化の形成および神経細胞死に関する因子の解析

    • Author(s)
      若佐谷保仁,瓦林毅,松原悦朗,東海林幹夫
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Book] 日本神経学会監修,「認知 症疾患治療ガイドライン」作成合同委員会編集2012

    • Author(s)
      東海林幹夫
    • Publisher
      医学書院
    • Related Report
      2012 Final Research Report
  • [Book] Alzheimer病(AD)の診断基準が新しく改定された画像診断における特徴的所見を教えてください.診断する上での注意点はありますか?2012

    • Author(s)
      東海林幹夫
    • Publisher
      認知症診療Q&A92中外医学社
    • Related Report
      2012 Final Research Report
  • [Book] 薬物治療.認知症:神経心理学的アプローチ.辻省次2012

    • Author(s)
      東海林幹夫
    • Publisher
      河村満編中山書店
    • Related Report
      2012 Final Research Report
  • [Book] アミロイドーシスへの濾過医を深めるための用語集.厚生労働科学研究費補助金難治性疾患克服研究事業2012

    • Author(s)
      東海林幹夫
    • Publisher
      アミロイドーシスに関する調査研究班(安東由起夫班長編)
    • Related Report
      2012 Final Research Report
  • [Book] Part3,アルツハイマー病2012

    • Author(s)
      東海林幹夫
    • Publisher
      別冊NHKきょうの健康「認知症」NHK出版
    • Related Report
      2012 Final Research Report
  • [Book] I.症候と鑑別診断,知的機能障害と認知症,今日の神経治療指針第2版(水澤英洋編)2012

    • Author(s)
      東海林幹夫
    • Publisher
      医学書院,東京
    • Related Report
      2012 Final Research Report
  • [Book] 認知症疾患治療ガイドライン2010.コンパクト版20122012

    • Author(s)
      東海林幹夫
    • Publisher
      医学書院
    • Related Report
      2012 Annual Research Report
  • [Book] 認知症診療Q&A2012

    • Author(s)
      東海林幹夫
    • Publisher
      中外医学社
    • Related Report
      2012 Annual Research Report
  • [Book] 認知症:神経心理学的アプローチ2012

    • Author(s)
      東海林幹夫
    • Publisher
      中山書店
    • Related Report
      2012 Annual Research Report
  • [Book] 今日の神経治療指針 第2版2012

    • Author(s)
      東海林幹夫
    • Publisher
      医学書院
    • Related Report
      2012 Annual Research Report
  • [Book] 別冊NHKきょうの健康「認知症」2012

    • Author(s)
      東海林幹夫
    • Publisher
      NHK出版
    • Related Report
      2012 Annual Research Report
  • [Book] アミロイドーシス診療のすべて-ガイドライン-完全詳解-.6脳アミロイドーシス(1)アルツハイマー病2011

    • Author(s)
      東海林幹夫
    • Publisher
      別冊・医学のあゆみ(山田正仁編)医歯薬出版社
    • Related Report
      2012 Final Research Report
  • [Book] 脳アミロイドーシスに対するAs免疫療法.アミロイドーシスuptodate2011

    • Author(s)
      東海林幹夫
    • Publisher
      別冊・医学のあゆみ(山田正仁編)医歯薬出版株式会社
    • Related Report
      2012 Final Research Report
  • [Book] 第16章,脳卒中による認知症,脳卒中の内科的治療.弘前大学出版会「脳を知る」シリーズ,第1巻「脳卒中を知る」佐藤敬2011

    • Author(s)
      東海林幹夫
    • Publisher
      若林孝一編弘前大学出版会
    • Related Report
      2012 Final Research Report
  • [Book] 認知症臨床研究の動向と展望.日本臨床増刊号認知症学(上)-その解明と治療の最新知見-2011

    • Author(s)
      東海林幹夫
    • Publisher
      日本臨床社
    • Related Report
      2012 Final Research Report
  • [Book] MCIとその概念,4) coversion と reversion.日本臨床増刊号 認知症学(下)-その解明と治療の最新知見-2011

    • Author(s)
      東海林幹夫
    • Publisher
      日本臨床社
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.h-shinnai.jp/

    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 神経変性疾患検査用バイオマーカーとその利用法2012

    • Inventor(s)
      東海林幹夫
    • Industrial Property Rights Holder
      東海林幹夫
    • Industrial Property Number
      2012-002178
    • Filing Date
      2012-11-14
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Overseas

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Published: 2011-08-05   Modified: 2019-07-29  

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