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Simultaneous analysis of Aβ oligomers, Aβ fibrils and phosphrylated tau protein using fluroine-MRI

Research Project

Project/Area Number 17H03560
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionShiga University of Medical Science

Principal Investigator

Tooyama Ikuo  滋賀医科大学, 医学部, 理事 (20207533)

Co-Investigator(Kenkyū-buntansha) 赤津 裕康  名古屋市立大学, 医薬学総合研究院(医学), 教授 (00399734)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords脳神経疾患 / アルツハイマー病 / 核磁気共鳴画像 / ベータアミロイド / アミロイドオリゴマー / タウタンパク / 診断 / 治療 / 脳神経 / タウ / 神経科学 / 認知症 / 神経化学 / タウプロテイン
Outline of Final Research Achievements

Molecular imaging is a useful method to detect brain regions in living patients with dementia. Although amyloid and tau imaging using positron emission tomography (PET) are clinically available, no clinical studies using magnetic resonance imaging (MRI) have been conducted. Recently, molecular imaging for dementia using Fluorine-19 (19F) MRI has received an attention. Because 19F displays an intense nuclear magnetic resonance (NMR) signal and is almost non-existent in the body, a target can be detected with a high signal-to-noise ratio using fluorinated contrast agents using fluorine-MRI. We have developed several probes for molecular imaging of dementia using fluorine-MRI. These include Shiga-X22 and Shiga-Y5 for amyloid imaging and Shiga-X35 for tau imaging. In addition, we describe double-MR images of Shiga-Y5 and Shiga-X22 in the brains of APP/PS1 mice using 19F chemical shift imaging in order to detect amyloid oligomers.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病モデルマウスを用いて、フッ素MR画像法においては、世界2例目となるアミロイドイメージグ、世界初となるタウイメージング、フッ素2重画像法による世界初のAβオリゴマーの画像化に成功した。フッ素MR画像法は、PETに比べ放射性同位体を使わない、くり返し測定が可能、サイクロトロンのような高価な施設がいらない、など利点が多い。多重フッ素MR画像法のように複数の病変を同時に画像化することも可能である。こうした点から、フッ素MR画像法は次世代の分子イメージング技術として期待されている。フッ素MR画像技術など革新的な基礎技術をわが国で開発しておくことは、国際競争に打ち勝つためにも重要である。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (41 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (5 results) Journal Article (14 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (19 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Patent(Industrial Property Rights) (3 results)

  • [Int'l Joint Research] マレーシア国民大学(マレーシア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] アリゾナ州立大学/バナーサンヘルス研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] マレーシア国民大学(マレーシア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] マレーシア国民大学(マレーシア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] サンヘルス研究所(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Keto form of curcumin derivatives strongly binds to Aβ oligomers but not fibrils2021

    • Author(s)
      Yanagisawa D, Kato T, Taguchi H, Shirai N, Hirao K, Sogabe T, Tomiyama T, Gamo K, Hirahara Y, Kitada M, Tooyama I
    • Journal Title

      Biomaterials

      Volume: 270 Pages: 120686-120686

    • DOI

      10.1016/j.biomaterials.2021.120686

    • NAID

      120006959909

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorine-19 Magnetic Resonance Imaging for Detection of Amyloid β Oligomers Using a Keto Form of Curcumin Derivative in a Mouse Model of Alzheimer’s Disease2021

    • Author(s)
      Yanagisawa Daijiro、Ibrahim Nor Faeizah、Taguchi Hiroyasu、Morikawa Shigehiro、Tomiyama Takami、Tooyama Ikuo
    • Journal Title

      Molecules

      Volume: 26 Issue: 5 Pages: 1362-1362

    • DOI

      10.3390/molecules26051362

    • NAID

      120007028249

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of transgenic cynomolgus monkeys overexpressing the gene for amyloid-β precursor protein2020

    • Author(s)
      Seita Y, Morimura T, Watanabe N, Iwatani C, Tsuchiya H, Nakamura S, Suzuki T, Yanagisawa D, Tsukiyama T, Nakaya M, Okamura E, Muto M, Ema M, Nishimura M, Tooyama I.
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: - Issue: 1 Pages: 45-60

    • DOI

      10.3233/jad-191081

    • NAID

      120006859791

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of FTMT Expression by Retinal Pigment Epithelial Cells on Features of Angiogenesis2020

    • Author(s)
      Buyandelger Undral、Walker Douglas G.、Yanagisawa Daijiro、Morimura Toshifumi、Tooyama Ikuo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 10 Pages: 3635-3635

    • DOI

      10.3390/ijms21103635

    • NAID

      120006862374

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel fluorinated derivative of curcumin negatively regulates thioredoxin-interacting protein expression in retinal pigment epithelial and macrophage cells2020

    • Author(s)
      Buyandelger Undral、Walker Douglas Gordon、Taguchi Hiroyasu、Yanagisawa Daijiro、Tooyama Ikuo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 532 Issue: 4 Pages: 668-674

    • DOI

      10.1016/j.bbrc.2020.08.114

    • NAID

      120006887065

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.2020

    • Author(s)
      Tsubaki H, Tooyama I, Walker DG
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 24 Pages: 9357-9357

    • DOI

      10.3390/ijms21249357

    • NAID

      120006951355

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of Proteome Profile in AβPP/PS1 Mice Hippocampus, Medial Prefrontal Cortex, and Striatum by Palm Oil Derived Tocotrienol-Rich Fraction.2019

    • Author(s)
      Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Makpol S, Wan Ngah WZ, Damanhuri HA, Tooyama I
    • Journal Title

      Alzheimers Dis.

      Volume: 72 Issue: 1 Pages: 229-246

    • DOI

      10.3233/jad-181171

    • NAID

      120006768262

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer’s disease and aged brains: increased levels correlate with neuropathology2019

    • Author(s)
      Mendsaikhan Anarmaa、Tooyama Ikuo、Bellier Jean-Pierre、Serrano Geidy E.、Sue Lucia I.、Lue Lih-Fen、Beach Thomas G.、Walker Douglas G.
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 7 Issue: 1 Pages: 215-215

    • DOI

      10.1186/s40478-019-0862-8

    • NAID

      120006777342

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice2018

    • Author(s)
      Durani Lina Wati、Hamezah Hamizah Shahirah、Ibrahim Nor Faeizah、Yanagisawa Daijiro、Nasaruddin Muhammad Luqman、Mori Masaki、Azizan Kamalrul Azlan、Damanhuri Hanafi Ahmad、Makpol Suzana、Wan Ngah Wan Zurinah、Tooyama Ikuo
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 64 Issue: 1 Pages: 249-267

    • DOI

      10.3233/jad-170880

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of aging rat2018

    • Author(s)
      Hamezah Hamizah Shahirah、Durani Lina Wati、Yanagisawa Daijiro、Ibrahim Nor Faeizah、Aizat Wan Mohd、Bellier Jean Pierre、Makpol Suzana、Ngah Wan Zurinah Wan、Damanhuri Hanafi Ahmad、Tooyama Ikuo
    • Journal Title

      Experimental Gerontology

      Volume: 111 Pages: 53-64

    • DOI

      10.1016/j.exger.2018.07.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y52018

    • Author(s)
      Yanagisawa Daijiro、Hamezah Hamizah Shahirah、Durani Lina Wati、Taguchi Hiroyasu、Tooyama Ikuo
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 12 Pages: e0208440-e0208440

    • DOI

      10.1371/journal.pone.0208440

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorine-19 magnetic resonance imaging probe for the detection of tau pathology in female rTg4510 mice2017

    • Author(s)
      Yanagisawa Daijiro、Ibrahim Nor Faeizah、Taguchi Hiroyasu、Morikawa Shigehiro、Kato Tomoko、Hirao Koichi、Shirai Nobuaki、Sogabe Takayuki、Tooyama Ikuo
    • Journal Title

      Journal of Neuroscience Research

      Volume: 96 Issue: 5 Pages: 841-851

    • DOI

      10.1002/jnr.24188

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions2017

    • Author(s)
      Hamezah Hamizah Shahirah、Durani Lina Wati、Ibrahim Nor Faeizah、Yanagisawa Daijiro、Kato Tomoko、Shiino Akihiko、Tanaka Sachiko、Damanhuri Hanafi Ahmad、Ngah Wan Zurinah Wan、Tooyama Ikuo
    • Journal Title

      Experimental Gerontology

      Volume: 99 Pages: 69-79

    • DOI

      10.1016/j.exger.2017.09.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Age-related changes in the metabolic profiles of rat hippocampus, medial prefrontal cortex and striatum2017

    • Author(s)
      Durani Lina Wati、Hamezah Hamizah Shahirah、Ibrahim Nor Faeizah、Yanagisawa Daijiro、Makpol Suzana、Damanhuri Hanafi Ahmad、Tooyama Ikuo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 3 Pages: 1356-1363

    • DOI

      10.1016/j.bbrc.2017.09.164

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] MRIを用いた認知症の分子イメージング2020

    • Author(s)
      遠山育夫、柳沢大治郎、田口弘康
    • Organizer
      第39回日本認知症学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Effect of genetic background on tau accumulation in rTg4510 mice2019

    • Author(s)
      Daijiro Yanagisawa, Hamizah Shahirah Hamezah, Aslina Pahrudin Arrozi, Hiroyasu Taguchi, Ikuo Tooyama
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Therapeutic effects of a curcumin derivative Shiga-Y5 in the brain of a mouse model of Alzheimer’s disease2019

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Ikuo Tooyama
    • Organizer
      第13回日中合同組織細胞化学セミナー
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] rTg4510マウスのタウ蓄積量を変動させる因子の探索2019

    • Author(s)
      柳沢 大治郎、Hamizah Shahirah Hamezah、Aslina Pahrudin Arrozi、遠山 育夫
    • Organizer
      第38回日本認知症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト組織切片を用いたアルツハイマー病の神経原線維変化に結合する新規化合物の探索2019

    • Author(s)
      加藤智子,柳沢大治郎,田口弘康,遠山育夫
    • Organizer
      第38回日本認知症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] :Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of APP/PS1 transgenic mice and its modulation by tocotrienol-rich fraction.2019

    • Author(s)
      Hamezah HS, Yanagisawa D, Durani LW, Ibrahim NF, Damanhuri HA, Ngah WZW, Tooyama
    • Organizer
      第46回日本脳科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Curcumin derivative with C-4 substituent attenuated amyloid deposition, but did not affect tau pathology in mouse models.2018

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Lina Wati Durani, Hamizah Shahirah, Hamezah, Ikuo Tooyama
    • Organizer
      Alzheimer’s Association International Conference 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of abnormal protein accumulation in Alzheimer’s disease using magnetic resonance imaging.2018

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Ikuo Tooyama
    • Organizer
      The 5th Annual Meeting of Mongolian Neuroscience Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] フッ素MRIによる脳内タウ凝集体の検出2018

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Shigehiro Morikawa, Tomoko Kato, Ikuo Tooyama
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of TRF on memory, proteome profile, and amyloid pathology in APP/PS1 mice2018

    • Author(s)
      Hamizah Shahirah Hamezah, Lina Wati Durani, Nor Faeizah Ibrahim, Daijiro Yanagisawa, Suzana Makpol, Hanafi Ahmad Damanhuri, Wan Zurinah Wan Ngah, Ikuo Tooyama
    • Organizer
      第37回日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] F-methyl-curcumin-1 (Shiga-Y5) はアルツハイマー病の画像診断や治療の候補化合物である2018

    • Author(s)
      遠山育夫、柳沢大治郎、田口弘康
    • Organizer
      第45回日本脳科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Application of double MR imaging for analysis of senile plaques and Aβ oligomers in the brain of APP/PS1 double transgenic mouse model of Alzheimer’s disease2017

    • Author(s)
      Ikuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi
    • Organizer
      中国微小脳循環学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tau imaging using fluorine-19 MRI in a mouse model of tauopathy2017

    • Author(s)
      Daijiro Yanagisawa, Nor Faeizah Ibrahim, Hiroyasu Taguchi, Shigehiro Morikawa, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Ikuo Tooyama
    • Organizer
      国際アルツハイマー病学会2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] F-methyl-curcumin-1 is a potential diagnostic and therapeutic agent for Alzheimer's disease2017

    • Author(s)
      Ikuo Tooyama, Anarmaa Mendsaikhan, Daijiro Yanagisawa, Hiroyasu Taguchi
    • Organizer
      第4回モンゴル神経科学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo detection of tau pathology by fluorine-19 MR imaging in a mouse model of tauopathy2017

    • Author(s)
      aijiro Yanagisawa, Nor Faeizah Ibrahim, Hiroyasu Taguchi, Shigehiro Morikawa, Ikuo Tooyama
    • Organizer
      第12回日本分子イメージング学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Application of double MR imaging for analysis of multiple pathological proteins in the brain of transgenic mouse model of Alzheimer’s disease2017

    • Author(s)
      kuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi
    • Organizer
      第44回日本脳科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] rain atrophy, cognitive functions and oxidative stress in aged rats.2017

    • Author(s)
      Hamizah Shahirah Hamezah, Lina Wati Durani, Nor Faeizah Ibrahima, Daijiro Yanagisawa, Tomoko Kato, Akihiko Shiinoa, Hanafi Ahmad Damanhuri, Wan Zurinah Wan Ngah, Ikuo Tooyama
    • Organizer
      第36回日本認知症学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ocotrienol-rich fraction derived palm oil alleviates cognitive impairment and alters metabolite profiling in AβPP/PS1 Alzheimer’s disease mice model2017

    • Author(s)
      Lina Wati Durani, Hamizah Shahirah Hamezah, Nor Faeizah Ibrahim, Daijiro Yanagisawa, Muhammad Luqman Nasaruddin, Masaki Mori, Hanafi Ahmad Damanhuri, Suzana Makpol, Wan Zurinah Wan Ngah, Ikuo Tooyama
    • Organizer
      第36回日本認知症学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] フッ素MRIによるタウ病変のイメージング2017

    • Author(s)
      柳沢大治郎、田口弘康、森川茂廣、遠山育夫
    • Organizer
      第36回日本認知症学会総会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] ミトコンドリアフェリチン発現誘導剤2020

    • Inventor(s)
      遠山育夫、柳沢大治郎、田口弘康
    • Industrial Property Rights Holder
      遠山育夫、柳沢大治郎、田口弘康
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-144256
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] チオレドキシン相互作用タンパク質発現抑制剤2020

    • Inventor(s)
      遠山育夫、田口弘康、柳沢大治郎
    • Industrial Property Rights Holder
      遠山育夫、田口弘康、柳沢大治郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-141272
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] アミロイドオリゴマーの画像診断薬2019

    • Inventor(s)
      遠山育夫、田口弘康、柳沢大次郎、加藤智子
    • Industrial Property Rights Holder
      滋賀医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-033405
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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