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Study of preclinical diagnosis and pre-emptive treatment trial for neurodegenerative dementia

Research Project

Project/Area Number 15K09820
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionTohoku University

Principal Investigator

Waragai Masaaki  東北大学, 加齢医学研究所, 非常勤講師 (50533775)

Research Collaborator 徳田 隆彦  京都府立医科大学, 大学院医学研究科分子脳病態解析学(神経内科), 教授 (80242692)
鈴木 利治  北海道大学, 薬学研究院, 教授 (80179233)
荒井 啓行  東北大学, 加齢医学研究所, 教授 (30261613)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsアルツハイマー病 / 血液バイオマーカーバイオマーカー / MRスペクトロスコピー / 後部帯状回 / 血液バイオマーカー / MRI / MRS / バイオマーカー / アルカデイン / アディポネクチン / パーキンソン病 / シヌクレイン / PMCA法 / 脳脊髄液 / 血清 / 神経原性変化 / タウ
Outline of Final Research Achievements

We studied early and easy diagnostic methods for Mild Cognitive Impairment(MCI) and Alzheimer's Disease(AD) using by blood based factors and usual 1.5T Magnetic Resonance Imaging(MRI) and spectroscopy(MRS) of the brain combined with cerebrospinal fluid(CSF) biomarkers amyloid beta and phosphorylated tau (p-tau) in clinical practice. We found that plasma p-tau level is significantly increased in patients with early AD and Down syndrome which have same brain pathology as AD. Thus, the plasma levels of p-tau may be used for good blood biomarker for screening subjects at risk of AD.
Furthermore, our longitudinal study of brain metabolites by MRS demonstrated that significant decreased N-acetylaspartate (NAA)/Myo-inositol(MI) ratio in the posterior cingulate gyri(PCG) not only in symptomatic AD but also preclinical AD.
Thus, we concluded that accurate measurement of plasma p-tau and amyloid beta together with decreased NAA/MI in the PCG could be used as useful peripheral AD biomarker.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Int'l Joint Research] Department of Neurosciences,/University of California,/San Diego(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Decreased N-Acetyl Aspartate/Myo-Inositol Ratio in the Posterior Cingulate Cortex Shown by Magnetic Resonance Spectroscopy May Be One of the Risk Markers of Preclinical Alzheimer's Disease: A 7-Year Follow-Up Study.2017

    • Author(s)
      Waragai M, Moriya M, Nojo T.
    • Journal Title

      J Alzheimers Dis

      Volume: 60 Issue: 4 Pages: 1411-1427

    • DOI

      10.3233/jad-170450

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome2017

    • Author(s)
      Tatebe Harutsugu、Kasai Takashi、Ohmichi Takuma、Kishi Yusuke、Kakeya Tomoshi、Waragai Masaaki、Kondo Masaki、Allsop David、Tokuda Takahiko
    • Journal Title

      Molecular Neurodegeneration

      Volume: 12 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s13024-017-0206-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Importance of adiponectin activity in the pathogenesis of Alzheimer's disease2017

    • Author(s)
      Waragai M, Ho G, Takamatsu Y, Sekiyama K, Sugama S, Takenouchi T, Masliah E, Hashimoto M
    • Journal Title

      Ann Clin Transl Neurol

      Volume: 4 Issue: 8 Pages: 591-600

    • DOI

      10.1002/acn3.436

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a Biochemical Diagnosis of Parkinson Disease by Detection of α-Synuclein Misfolded Aggregates in Cerebrospinal Fluid.2017

    • Author(s)
      Shahnawaz M, Tokuda T, Waragai M, Mendez N, Ishii R, Trenkwalder, Mollenhauer B, Soto C C,
    • Journal Title

      JAMA Neurol

      Volume: 74 Issue: 2 Pages: 163-172

    • DOI

      10.1001/jamaneurol.2016.4547

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insight into the dissociation of behavior from histology in Synucleinopathies and in related neurodegenerative diseases2016

    • Author(s)
      Sekiyama K, Takamatsu Y, Koike W, Waragai M, Takenouchi T, Sugama S, Hashimoto M.
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: in press Issue: 3 Pages: 831-841

    • DOI

      10.3233/jad-151015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease.2016

    • Author(s)
      Waragai M, Adame A, Trinh I, Sekiyama K, Takamatsu Y, Une K, Masliah E, Hashimoto M
    • Journal Title

      J Alzheimers Dis.

      Volume: in press Issue: 4 Pages: 1453-1459

    • DOI

      10.3233/jad-151116

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of dementia by acrolein, amyloid-β and creatinine.2015

    • Author(s)
      Igarashi K, Yoshida M, Waragai M, Kashiwagi K
    • Journal Title

      Clin Chim Acta

      Volume: 450 Pages: 56-63

    • DOI

      10.1016/j.cca.2015.07.017

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Abnormalities of MRS of the Posterior Cingulate Cortex May Precede onset of MCI Due to Alzheimer’s Diseases -Five Years Follow up Study of 277 Cognitive Normal Elderly Subjects-2017

    • Author(s)
      Masaaki Waragai, Masaru Moriya
    • Organizer
      Alzheimer’s Association International Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日常診療でのVSRAD及びMRSを用いたアルツハイマー病の早期スクリーニングの有用性2015

    • Author(s)
      藁谷正明
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      リンクステーションホール青森 第4会場、青森県、青森市
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Disease Modifying Effect of Adiponectin in Model of a-Synucleinopathies in Vitro and in Vivo2015

    • Author(s)
      Masaaki Waragai, Kazunari Sekiyama, Yoshiki Takamatsu, Masayo FujitaAkio Sekigawa, Naomichi Iwai , Edward Rockenstein , Satoshi Inoue, Albert R. La Spada, Elizer Masliah, Makoto Hashimoto
    • Organizer
      Alzheimer's Association International Conference (AAIC2015)
    • Place of Presentation
      Washington, DC United States
    • Year and Date
      2015-07-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2022-01-24  

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