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Identification of target molecules related the progression of Alzheimer's disease

Research Project

Project/Area Number 24310144
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Medical genome science
Research InstitutionNiigata University

Principal Investigator

KUWANO Ryozo  新潟大学, 脳研究所, フェロー (20111734)

Co-Investigator(Kenkyū-buntansha) IKEUCHI Takeshi  新潟大学, 脳研究所, 教授 (20372469)
Co-Investigator(Renkei-kenkyūsha) MIYASHITA Akinori  新潟大学, 脳研究所, 助教 (60323995)
NAKAYA Akihiro  新潟大学, 研究推進機構, 准教授 (60301149)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Keywordsアルツハイマー病 / ゲノム / 脳組織 / ターゲット分子 / 染色体 / 培養細胞 / 遺伝子発現 / リスク遺伝子 / 老人斑 / 神経原繊維変化 / 次世代シークエンサー / RNA
Outline of Final Research Achievements

Major neuropathological features of Alzheimer’s disease are senile plaques and neurofibrillary tangles .To identify genes relevant to neuropathological expansion defined by the Braak stage, we conducted whole-genome exon array analysis with 213 human postmortem brain tissues from the entorhinal, temporal and frontal cortices of 71 brain-donor subjects. We identified eight mRNAs and 5 non-coding RNAs associated with the progression of the characteristic lesion of Alzheimer’ disease brain diagnosed by Braak stage.We hypothesized that the phenotype-associated SNPs may spatially contact with distal genomic loci and may lead to regulate the gene expression. To analyze the relationship between the gene expression profiles by exon array and the higher-order chromatin structure data, we used the tethered conformation capture (TCC) method in the human neuroblastoma cell line, SK-N-SH, and the glioma cell line, U-251MG.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report

Research Products

(17 results)

All 2015 2014 2013 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] A Second Pedigree with Amyloid-less Familial Alzheimer's Disease Harboring an Identical Mutation in the <i>Amyloid Precursor Protein</i> Gene (E693delta)2015

    • Author(s)
      Kutoku Y ほか
    • Journal Title

      Intern. Med.

      Volume: Epub Issue: 2 Pages: 205-208

    • DOI

      10.2169/internalmedicine.54.3021

    • NAID

      130004903009

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Lack of genetic association between TREM2 and late-onset Alzheimer’s disease in a Japanese population2014

    • Author(s)
      Akinori Miyashitaa, Yanan Wen 他
    • Journal Title

      J Alzheimers Dis.

      Volume: 印刷中 Pages: 1031-1038

    • DOI

      10.3233/jad-140225

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genes associated with the progression of neurofibrillary tangles in Alzheimer’s disease2014

    • Author(s)
      Miyashita A ほか
    • Journal Title

      Translational Psychiatry

      Volume: 4

    • DOI

      10.1038/tp.2014.35

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PLXNA4 is associated with Alzheimer disease and modulates tau phosphorylation2014

    • Author(s)
      Jun G ほか
    • Journal Title

      Ann Neurol

      Volume: 76 Pages: 379-392

    • DOI

      10.1002/ana.24219

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and neuroimaging features of patient with early-onset Parkinson's disease with dementia carrying SNCA p.G51D mutation.2014

    • Author(s)
      Tokutake T, Ishikawa A, Yoshimura N, Miyashita A, Kuwano R, Nishizawa M, Ikeuchi T
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 20 Pages: 262-264

    • DOI

      10.1016/j.parkreldis.2013.11.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relative Ratio and Level of Amyloid-β 42 Surrogate in Cerebrospinal Fluid of Familial Alzheimer Disease Patients with Presenilin 1 Mutations2014

    • Author(s)
      Tagami et al.
    • Journal Title

      Neurodegener Dis. .

      Volume: 13 Pages: 166-170

    • DOI

      10.1159/000355258

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] SORL1 is genetically associated with neuropathologically characterized late-onset Alzheimer's disease2013

    • Author(s)
      Wen Y, Miyashita A, Kitamura N, Tsukie T, Saito Y, Hatsuta H, Murayama S, et al.
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 35(2) Pages: 387-387

    • DOI

      10.3233/jad-122395

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [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

    • DOI

      10.1371/journal.pone.0058618

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 15. Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease2013

    • Author(s)
      Kikuchi M, Ogishima S, Miyamoto T, Miyashita A, Kuwano R, Nakaya J, Tanaka H
    • Journal Title

      PLoS ONE

      Volume: 8

    • DOI

      10.1371/journal.pone.0076162

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebrospinal fluid levels of phosphorylated tau and Aβ1-38/Aβ1-40/Aβ1-42 in Alzheimer's disease with PS1 mutations.2013

    • Author(s)
      Ikeda M, Yonemura K, Kakuda S, Tashiro Y, Fujita Y, Takai E, Hashimoto Y, Makioka K, Furuta N, Ishiguro K, Maruki R, Yoshida J, Miyaguchi O, Tsukie T, Kuwano R, Yamazaki T, Yamaguchi H, Amari M, Takatama M, Harigaya Y, Okamoto K
    • Journal Title

      Amyloid

      Volume: 20 Pages: 107-112

    • DOI

      10.3109/13506129.2013.790810

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒト剖検脳を用いたアルツハイマー病関連マイクロRNAの解析.2014

    • Author(s)
      原範和、菊地正隆、宮下哲典、初田裕幸、齊藤祐子、村山 繁雄、赤津裕康、池内健、桑野良三
    • Organizer
      日本認知症学会
    • Place of Presentation
      横浜パシフィコ
    • Year and Date
      2014-11-29 – 2014-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] アルツハイマー病における生体分子間ネットワーク解析手法の提案2014

    • Author(s)
      菊地正隆, 原範和, 宮下哲典, 初田裕幸, 齊藤祐子, 村山繁雄, 池内健, 桑野良三
    • Organizer
      日本認知症学会
    • Place of Presentation
      横浜パシフィコ
    • Year and Date
      2014-11-27 – 2014-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞特異的な遺伝子発現は染色体高次構造の影響を受けるのか?2014

    • Author(s)
      菊地正隆, 長谷川舞衣, 原 範和, 宮下哲典, 中谷明弘, 池内健, 桑野良三
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜パシフィコ
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genes associated with the progression of neurofibrillary tangles in Alzheimer’s disease brains2014

    • Author(s)
      Miyashita A, Kuwano R, Hatsuta H, Kikuchi M, Nakaya A, Saito Y, Tsukie T, Hara N, Ogishima S, Kakita A, Takahashi H, Murayama S, Ihara, Ikeuchi T
    • Organizer
      AAIC
    • Place of Presentation
      Bella Center, Copenhagen, Denmark
    • Year and Date
      2014-07-11 – 2014-07-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] SORL1 is Genetically Associated With Late-Onset Alzheimer's Disease in Japanese, Koreans and Caucasians.2013

    • Author(s)
      Miyashita A, Kuwano R, Schellenberg G, Ihara Y, Kanazawa I, Tsuji S, Yamamoto K, Tokunaga K, Nishida N, Yoshida M, Pericak-Vance M, Haines J, Mayeux R, St. George-Hyslop P, Kim JW, Takahashi S, Wang LS, Jun G, Koike A, Farrer L
    • Organizer
      AAIC
    • Place of Presentation
      アメリカ、ボストン
    • Related Report
      2013 Annual Research Report
  • [Presentation] 細胞特異的なゲノム高次構造解析法の検討2013

    • Author(s)
      長谷川 舞衣, 原 範和, 菊地 正隆, 宮下 哲典, 中谷 明弘, 池内 健, 桑野 良三
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] 認知症の表現型を説明する遺伝子解析の試み

    • Author(s)
      桑野良三
    • Organizer
      第18回日本認知神経科学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2012-04-23   Modified: 2019-07-29  

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