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Development of blood biomarkers for Alzheimer's disease using high sensitivity digital ELISA method

Research Project

Project/Area Number 18K15461
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology (2020)
Kyoto Prefectural University of Medicine (2018-2019)

Principal Investigator

Tatebe Harutsugu  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 研究員(任常) (00637027)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血液バイオマーカー / 認知症 / リン酸化タウ / 高感度ELISA / アルツハイマー病 / 体液バイオマーカー / ニューロフィラメント / Simoa / バイオマーカー / p-tau / tau / NFL / TDP-43 / デジタルELISA / 神経変性疾患
Outline of Final Research Achievements

We have introduced Simoa (Single molecular array), an ultrasensitive digital assay technology, to introduce phosphorylated tau (p-tau), one of the Alzheimer's disease (AD) biomarkers, in human blood for the first time in the world. We have developed a quantitative system that can be detected on the order of fg/mL.
In addition to p-tau, we have multicenter blood and cerebrospinal fluid for other core biomarkers of AD, Aβ40, Aβ42, t-Tau (total tau protein), NF-L (neurofilament light chain). Sample measurements were taken. As a result, it was confirmed that all substances can be stably measured with Simoa.

Academic Significance and Societal Importance of the Research Achievements

我々は、超高感度デジタルアッセイ技術であるSimoaを用いて、ヒトの血液中でアルツハイマー病(AD)バイオマーカーを測定する方法の開発をおこなってきた。
血液検査でAD特異的な物質を測定することに成功している。今後、認知症診断において簡便で安価な検査方法として、この血液バイオマーカーを利用できる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Cerebral spinal fluid biomarker profiles in CNS infection associated with HSV and VZV mimic patterns in Alzheimer’s disease2021

    • Author(s)
      Shinomoto Makiko、Kasai Takashi、Tatebe Harutsugu、Kitani-Morii Fukiko、Ohmichi Takuma、Fujino Yuzo、Allsop David、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      Translational Neurodegeneration

      Volume: 10 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s40035-020-00227-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantification of Blood Caffeine Levels in Patients With Parkinson's Disease and Multiple System Atrophy by Caffeine ELISA2020

    • Author(s)
      Ohmichi Takuma、Kasai Takashi、Shinomoto Makiko、Matsuura Jun、Koizumi Takashi、Kitani-Morii Fukiko、Tatebe Harutsugu、Sasaki Hidenao、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      Frontiers in Neurology

      Volume: 11 Pages: 580127-580127

    • DOI

      10.3389/fneur.2020.580127

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intrathecal nusinersen treatment after ventriculo-peritoneal shunt placement: A case report focusing on the neurofilament light chain in cerebrospinal fluid2020

    • Author(s)
      Tozawa Takenori、Kasai Takashi、Tatebe Harutsugu、Shiomi Kozue、Nishio Hisahide、Tokuda Takahiko、Chiyonobu Tomohiro
    • Journal Title

      Brain and Development

      Volume: 42 Issue: 3 Pages: 311-314

    • DOI

      10.1016/j.braindev.2019.12.006

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS2019

    • Author(s)
      Takashi Kasai, Yuta Kojima, Takuma Ohmichi, Harutsugu Tatebe, Yukiko Tsuji, Yu-Ichi Noto, Fukiko Kitani-Morii, Makiko Shinomoto, David Allsop,Toshiki Mizuno, Takahiko Tokuda
    • Journal Title

      Annals of Clinical Translational Neurology

      Volume: 6 Issue: 12 Pages: 2489-2502

    • DOI

      10.1002/acn3.50943

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proteomic Profiling of Extracellular Vesicles Isolated From Cerebrospinal Fluid of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy2019

    • Author(s)
      Muraoka Satoshi、Jedrychowski Mark P.、Tatebe Harutsugu、DeLeo Annina M.、Ikezu Seiko、Tokuda Takahiko、Gygi Steven P.、Stern Robert A.、Ikezu Tsuneya
    • Journal Title

      Frontiers in Neuroscience

      Volume: 13 Pages: 1059-1059

    • DOI

      10.3389/fnins.2019.01059

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influx of Tau and Amyloid-β Proteins into the Blood During Hemodialysis as a Therapeutic Extracorporeal Blood Amyloid-β Removal System for Alzheimer’s Disease2019

    • Author(s)
      Kitaguchi Nobuya、Tatebe Harutsugu、Sakai Kazuyoshi、Kawaguchi Kazunori、Matsunaga Shinji、Kitajima Tomoko、Tomizawa Hiroshi、Kato Masao、Sugiyama Satoshi、Suzuki Nobuo、Mizuno Masao、Takechi Hajime、Nakai Shigeru、Hiki Yoshiyuki、Kushimoto Hiroko、Hasegawa Midori、Yuzawa Yukio、Tokuda Takahiko
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 69 Issue: 3 Pages: 687-707

    • DOI

      10.3233/jad-190087

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma neurofilament light chain: A potential prognostic biomarker of dementia in adult Down syndrome patients2019

    • Author(s)
      Shinomoto Makiko、Kasai Takashi、Tatebe Harutsugu、Kondo Masaki、Ohmichi Takuma、Morimoto Masafumi、Chiyonobu Tomohiro、Terada Naoto、Allsop David、Yokota Isao、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 4 Pages: e0211575-e0211575

    • DOI

      10.1371/journal.pone.0211575

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantification of brain-derived extracellular vesicles in plasma as a biomarker to diagnose Parkinson's and related diseases2019

    • Author(s)
      Ohmichi Takuma、Mitsuhashi Masato、Tatebe Harutsugu、Kasai Takashi、Ali El-Agnaf Omar M.、Tokuda Takahiko
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 61 Pages: 82-87

    • DOI

      10.1016/j.parkreldis.2018.11.021

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biomarker repurposing: Therapeutic drug monitoring of serum theophylline offers a potential diagnostic biomarker of Parkinson’s disease2018

    • Author(s)
      Ohmichi Takuma、Kasai Takashi、Kosaka Tadashi、Shikata Keisuke、Tatebe Harutsugu、Ishii Ryotaro、Shinomoto Makiko、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 7 Pages: e0201260-e0201260

    • DOI

      10.1371/journal.pone.0201260

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] THE EXPRESSION OF MICROTUBULE ASSOCIATED PROTEIN TAU IN MICE PODOCYTE2021

    • Author(s)
      Tomohiro Miyasaka, Jiarui Chang, Zhiwei Yao, Satoko Wada-Kakuda, Harutsugu Tatebe, Takahiko Tokuda
    • Organizer
      15th International Conference on Alzheimer‘s & Parkinson‘s Diseases
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス腎臓における微小管結合タンパク質タウの発現2020

    • Author(s)
      宮坂 知宏, 常 嘉瑞, 姚 シビ, 角田 聡子, 建部 陽嗣, 徳田 隆彦
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成人ダウン症候群患者の血漿NfL上昇とApoEフェノタイプの関係2020

    • Author(s)
      笠井 高士, 篠本 真紀子, 建部 陽嗣, 森井 芙貴子, 大道 卓摩, 近藤 正樹, 水野 敏樹, 徳田 隆彦
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血液バイオマーカーの進歩 認知症の多項目血液バイオマーカー2020

    • Author(s)
      徳田 隆彦, 建部 陽嗣
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] VPシャント留置後のヌシネルセン治療による髄液中neurofilament light-chainの経時的変化2020

    • Author(s)
      戸澤 雄紀, 千代延 友裕, 笠井 高士, 建部 陽嗣, 西尾 久英
    • Organizer
      第62回日本小児神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成人ダウン症候群の認知症診断と認知機能予後予測における血液バイオマーカーの有効性2020

    • Author(s)
      篠本 真紀子, 笠井 高士, 建部 陽嗣, 近藤 正樹, 大道 卓摩, 水野 敏樹, 徳田 隆彦
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成人ダウン症候群の認知症診断と認知機能予後予測における血液バイオマーカーの有効性2019

    • Author(s)
      笠井 高士, 篠本 真紀子, 建部 陽嗣, 近藤 正樹, 大道 卓摩, 水野 敏樹, 徳田 隆彦
    • Organizer
      第39回日本認知症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 超高感度ELISA(Simoa)による認知症の血液バイオマーカーの開発:リン酸化タウを中心に2019

    • Author(s)
      徳田 隆彦, 建部 陽嗣, 笠井 高士
    • Organizer
      第37回日本神経治療学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] パーキンソン病と関連疾患に関する有望なバイオマーカーとしての血漿中の脳由来エキソソーム2019

    • Author(s)
      大道 卓摩, 三橋 将人, 建部 陽嗣, 笠井 高士, 水野 敏樹, 徳田 隆彦
    • Organizer
      第13回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト血漿中リン酸化タウ蛋白の新規定量系の開発とアルツハイマー病の血液診断への応用2018

    • Author(s)
      建部 陽嗣, 大道 卓摩, 笠井 高士, 近藤 正樹, 藁谷 正明, David Allsop, 徳田 隆彦
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Brain-derived exosomes as potential blood biomarkers for Parkinson's disease and parkinsonism2018

    • Author(s)
      大道 卓摩, 三橋 将人, 建部 陽嗣, 笠井 高士, 水野 敏樹, 徳田 隆彦
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] ダウン症候群における血漿中総タウ濃度およびリン酸化タウ濃度は年齢依存性に増加する2018

    • Author(s)
      笠井 高士, 徳田 隆彦, 建部 陽嗣, 近藤 正樹, 石井 亮太郎, 大道 卓摩, 中川 正法, 水野 敏樹
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 成人期ダウン症候群における血漿中リン酸化タウ濃度上昇は認知症発症を予測する2018

    • Author(s)
      笠井 高士, 徳田 隆彦, 建部 陽嗣, 近藤 正樹, 石井 亮太郎, 大道 卓摩, 中川 正法, 水野 敏樹
    • Organizer
      第37回日本認知症学会学術大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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