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Non-biased expression analysis to search for molecules associated with amyloid-beta induced hyperphosphorylation of tau

Research Project

Project/Area Number 23591234
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionNiigata University

Principal Investigator

IKEUCHI Takeshi  新潟大学, 脳研究所, 教授 (20372469)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords脳神経疾患 / 遺伝子発現 / シグナル伝達 / 認知症 / アルツハイマー病 / アミロイド / タウ / リン酸化
Research Abstract

Senile plaque and neurofibrillary tangle are pathological hallmarks of brains of Alzheimer's disease. Senile plaque consists of amyloid-beta (Abeta) and neurofibrillary tangle is composed of hyperphosphorylated tau. The mechanism by which Abeta induces hyperphosphorylation of tau remains unclear. In this study, we addressed this question by establishing coculture system in which Abeta-induced hyperphosphorylation of tau is recapitulated. Total RNA was extracted from primary cultured neurons in which hyperphosphorylation of tau is induced by physiologically secreted Abeta by coculture system. By conducting unbiased examination using RNA expression array, we found that expressions in several genes are altred in condition where hyperphosphorylation of tau occurred in primary neurons. Bioinformatics analysis revealed that genes of altered expression affect insulin signaling.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (36 results)

All 2014 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 18 results,  Open Access: 1 results) Presentation (16 results) (of which Invited: 4 results)

  • [Journal Article] Lack of genetic association between TREM2 and late-onset Alzheimer’s disease in the Japanese population2014

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

      Journal of Alzheimer's Disease

      Volume: 印刷中

    • 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

      Neurodegenerative Disease

      Volume: 13 Issue: 2-3 Pages: 166-170

    • DOI

      10.1159/000355258

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasian2013

    • Author(s)
      Miyashita A, Koike A, Jun G, Wang LS, Takahashi S, Matsubara E, Kawarabayashi T, Shoji M, Tomita N, Arai H, Asada T, Harigaya Y, Ikeda M, Amari M, Hanyu H, Higuchi S, Ikeuchi T, Nishizawa M, Suga M, Kawase Y, Akatsu H, Kosaka K, Yamamoto T, Imagawa M, Hamaguchi T, Yamada M, Moriaha T, Takeda M, Takao T, Nakata K, Fujisawa Y, Sasaki K, Watanabe K, Nakashima K, Urakami K, Ooya T, Takahashi M, Yuzuriha T, Serikawa K, Yoshimoto S, Nakagawa R, Kim JW, Ki CS, Won HH, Na DL, Seo SW, Mook-Jung I; Alzheimer Disease Genetics Consortium, St George-Hyslop P, Mayeux R, Haines JL, Pericak-Vance MA, Yoshida M, Nishida N, Tokunaga K, Yamamoto K, Tsuji S, Kanazawa I, Ihara Y, Schellenberg GD, Farrer LA, Kuwano R
    • Journal Title

      PLOS One

      Volume: 8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extensive aggregation ofα-synuclein and tau in juvenile-onset neuroaxonal dystrophy : an autopsied individual with a novel mutation in the PLA2G6 gene-splicing site2013

    • Author(s)
      Riku Y, Ikeuchi T, Yoshino H, Mimuro M, Mano K, Goto Y, Hattori N, Sobue G, Yoshida M
    • Journal Title

      Acta Neuropathologica Communication

      Volume: 1 Pages: 12-12

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene2013

    • Author(s)
      Shimizu H, Toyoshima Y, Yokoseki A, Shiga A, Arakawa K, Sekine Y, Shimohata T, Ikeuchi T, Nishizawa M, Kakita A, Onodera O, Takahashi H.
    • Journal Title

      Acta Neuropathologica

      Volume: 126 Pages: 453-459

    • Related Report
      2013 Final 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 Issue: 4 Pages: e58618-e58618

    • DOI

      10.1371/journal.pone.0058618

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteredγ-secretase activity in mild cognitive impairment and Alzheimer's disease2012

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

      EMBO Molecular Medicine

      Volume: 4 Pages: 344-352

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autosomal dominant tauopathy with parkinsonism and central hypoventilation2012

    • Author(s)
      Omoto M, Suzuki S, Ikeuchi T, Ishihara T, Kobayashi T, Tsuboi Y, Ogasawara J, Koga M, Kawai M, Iwaki T, Kanda T
    • Journal Title

      Neurology

      Volume: 78 Pages: 752-764

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parkinsonian features in a patient with diffuse neurofibrillary tangles with calcification (DNTC)2012

    • Author(s)
      Ikeuchi T, Katsui T, Kasuga K, Hirose M, Nishizawa M
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 18 Pages: 649-650

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Coordinated increase levels of severalγ-secretase product peptides in the CSF of a subpopulation of sporadic Alzheimer's disease subjects2012

    • Author(s)
      Hata S, Taniguchi M, Piao Y, Ikeuchi T, Fagan AM, Holtzman DM, Bateman R, Gandy S, Urakami K, Suzuki T, Japanese Alzheimer's Disease Neuroimaging Initiatives
    • Journal Title

      Molecular Neurodegeneration

      Volume: 7 Pages: 16-16

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hyperphosphorylation of tau induced by naturally secreted amyloid-βat low nanomolar concentrations is modulated by insulin-dependent Akt-GSK3βsignaling pathway2012

    • Author(s)
      Tokutake T, Kasuga K, Yajima R, Sekine Y, Tezuka T, Nishizawa M, Ikeuchi T
    • Journal Title

      Journal of Biological Chemistry

      Volume: 287 Pages: 35222-35233

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a TPR-like domain in the Nicastrin subunit ofγ-secretase using synthetic antibodies2012

    • Author(s)
      Zhang X, Hoey RJ, Lin G, Koide A, Leung B, Ahn K, Dolios G, Paduch M, Ikeuchi T, Wang R, Li Y, Koide S, Sisodia SS
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Pages: 8534-8539

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel G37V mutation of SOD1 gene in autopsied patient with familial amyotrophic lateral sclerosis2012

    • Author(s)
      Kobayashi J, Kuroda M, Kawata A, Mochizuki Y, Mizutani T, Komori T, Ikeuchi T, Koide R
    • Journal Title

      Amyotrophic Lateral Sclerosis

      Volume: 14 Pages: 570-572

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hyperphosphorylation of tau induced by naturally secreted amyloid-b at low nanomolar concentrations is modulated by insulin-dependent Akt-GSK3 signaling pathway2012

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

      J Biol Chem

      Volume: 287 Issue: 42 Pages: 35222-35233

    • DOI

      10.1074/jbc.m112.348300

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of a TPR-like domain in the Nicastrin subunit of g-secretase using synthetic antibodies.2012

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

      Proc Natl Acad Sci USA

      Volume: 109 Issue: 22 Pages: 8534-8539

    • DOI

      10.1073/pnas.1202691109

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics and evidence for a common founder in Japanese families with MAPT R406W mutation.2011

    • Author(s)
      Ikeuchi T et al.
    • Journal Title

      Dementia Geriatric Cognitive Disorders EXTRA

      Volume: 1 Pages: 267-275

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predominant executive cognitive deficit and cerebral white matter lesion in a patient with fragile X-associated tremor/ataxia syndrome (FXTAS)2011

    • Author(s)
      Kasuga K et al.
    • Journal Title

      Case Reports in Neurology

      Volume: 3 Pages: 118-123

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Coordinated increase of g-secretase products in the plasma of some female Japanese sporadic Alzheimer’s disease patients: quantitative analysis of p3-Alc with a new ELISA system.2011

    • Author(s)
      Konno T et al.
    • Journal Title

      Molecular Neurodegeneration

      Volume: 6 Pages: 76-76

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cerebral small-vessel disease protein HTRA1 controls TGF-b1 signaling via cleavage of proTGF-b1.2011

    • Author(s)
      Shiga A et al.
    • Journal Title

      Human Molecular Genetics

      Volume: 20 Pages: 1800-1810

    • Related Report
      2011 Research-status Report
  • [Journal Article] Genotype-phenotype correlations in early onset ataxia with ocular motor apraxia and hypoalbuminemia.2011

    • Author(s)
      Yokoseki A et al.
    • Journal Title

      Brain

      Volume: 134 Pages: 1387-1399

    • Related Report
      2011 Research-status Report
  • [Presentation] アルツハイマー病の未病診断2013

    • Author(s)
      池内健
    • Organizer
      第32回分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 代謝恒常性の破綻によるアルツハイマー病の発症機序と新規治療法開発2013

    • Author(s)
      池内健
    • Organizer
      第3回日本認知症予防学会
    • Place of Presentation
      新潟市
    • Year and Date
      2013-09-29
    • Related Report
      2013 Final Research Report
  • [Presentation] An emerging role of insulin resistance in amyloid-beta cascade hypothesis2013

    • Author(s)
      Ikeuchi T
    • Organizer
      The 20th IAGG World Congress of Gerontology and Geriatrics
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2013-06-24
    • Related Report
      2013 Final Research Report
  • [Presentation] Aβにより生じるタウリン酸化はインスリン依存性Akt-GSK3βシグナル障害が関連する2012

    • Author(s)
      徳武孝允,手塚敏之,関根有美,矢島隆二,春日健作,西澤正豊,池内健
    • Organizer
      第31回日本認知症学会
    • Place of Presentation
      つくば市(ポスター発表)
    • Year and Date
      2012-10-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Hyperphosphorylation of tau induced by naturally secreted amyloid-βat low nanomolar concentrations is mediated by insulin-dependent signaling pathway2012

    • Author(s)
      Tokutake T, Kasuga K, Yajima R, Sekine Y, Tezuka T, Nishizawa M, Ikeuchi T
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2012-10-16
    • Related Report
      2013 Final Research Report
  • [Presentation] βアミロイド依存性タウ・リン酸化におけるインスリン抵抗性の関与:初代神経培養細胞を用いた共培養による解析2012

    • Author(s)
      徳武孝允,池内健,春日健作,矢島隆二,西澤正豊
    • Organizer
      第53回日本神経学会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] アルツハイマー病の発症機構における糖尿病の関与2011

    • Author(s)
      池内健
    • Organizer
      第30回認知症学会.シンポジウム5「生活習慣病と認知症」
    • Place of Presentation
      東京
    • Year and Date
      2011-11-11
    • Related Report
      2013 Final Research Report
  • [Presentation] 共培養システムを用いたβアミロイド依存性タウリン酸化の解析:インスリンシグナル伝達障害の関与2011

    • Author(s)
      徳武孝允,春日健作,矢島隆二,西澤正豊,池内健
    • Organizer
      第30回日本認知症学会
    • Place of Presentation
      東京(ポスター発表)
    • Year and Date
      2011-11-11
    • Related Report
      2013 Final Research Report
  • [Presentation] β-amyloid induced hyperphosphorylation of tau : possible involvement of insulin signal dysfunction2011

    • Author(s)
      Tokutake T, Kasuga K, Yajima R, Nishizawa M, Ikeuchi T
    • Organizer
      Alzheimer's Association International Conference
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-20
    • Related Report
      2013 Final Research Report
  • [Presentation] βアミロイドによる誘発されるタウリン酸化におけるインスリンシグナル障害の関与2011

    • Author(s)
      徳武孝允,池内健,春日健作,矢島隆二,石原智彦,西澤正豊
    • Organizer
      第52回日本神経学会
    • Place of Presentation
      名古屋(口演発表)
    • Year and Date
      2011-05-19
    • Related Report
      2013 Final Research Report
  • [Presentation] アルツハイマー病患者・髄液中における可溶性LR11の増加2011

    • Author(s)
      池内健,他
    • Organizer
      第52回日本神経学会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] アルツハイマー病の発症機構における糖尿病の関与2011

    • Author(s)
      池内健
    • Organizer
      第30回日本認知症学会(招待講演)
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] An emerging role of insulin resistance in amyloid-beta cascade hypothesis

    • Author(s)
      Takeshi Ikeuchi
    • Organizer
      IAGG World Congress of Gerontology and Geriatrics
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病の未病診断

    • Author(s)
      池内 健
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 代謝恒常性の破綻によるアルツハイマー病の発症機序と新規治療法開発

    • Author(s)
      池内 健
    • Organizer
      日本認知症予防学会
    • Place of Presentation
      新潟市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] HDLSの分子病態と白質を主病変とする他疾患との鑑別

    • Author(s)
      池内 健
    • Organizer
      第53回 日本神経学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited

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

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