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The research of pathological condition for clinical diagnosis of tangle only dementia

Research Project

Project/Area Number 17K08725
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionNagoya City University

Principal Investigator

Hiroyasu Akatsu  名古屋市立大学, 医薬学総合研究院(医学), 教授 (00399734)

Co-Investigator(Kenkyū-buntansha) 正木 克由規  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00365652)
兼松 孝好  名古屋市立大学, 医薬学総合研究院(医学), 講師 (20381824)
田中 創始  名古屋市立大学, 医薬学総合研究院(医学), 講師 (30433220)
大原 弘隆  名古屋市立大学, 医薬学総合研究院(医学), 教授 (80285212)
間辺 利江  帝京大学, 医学部, 助教 (50723110)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords高齢者タウオパチ― / 補体 / 鉄 / 神経源線維変化 / 嗜銀顆粒 / 高齢者タウオパチー / 神経原線維変化 / 脳・神経
Outline of Final Research Achievements

In our institute, the autopsy of about 30 cases per year was continued. And the clinical and pathological data collection was completed. Immunostaining of accumulated cases, tangle only dementia confirmed by clinical neuropathological examination, was performed mainly for complement-related and iron metabolism-related markers.
The search for blood diagnostic markers has established a new cohort system. A new candidate factor for the diagnosis of Alzheimer's disease in blood markers was identified with collaboration. We have begun to investigate whether there is any diagnostic significance in clinical tauopathy patients including these. In addition, we have begun developing experiments in vitro level in order to purify denatured tau proteins and examine their potential for inflammation.

Academic Significance and Societal Importance of the Research Achievements

高齢者タウオパチーは、世界的に進むアルツハイマー病(AD)の画像病理相関研究において、ADの原因とされているアミロイド(Aβ)沈着を認めないケースとして注目されている。臨床的にADと誤診されやすいく、Aβ除去を狙った治療が無効となる。ADの血液での診断は困難とされたが、我々はその可能性を世界で始めて報告した。本研究では網羅的に臨床データ、凍結脳を用いた発現遺伝子解析・質量分析と、固定脳での免疫染色を駆使して高齢者タウオパチーの病態解析、変性タウ蛋白の挙動解析を進めている。社会的意義にまでつながる結果には至っていないが、現状の体制での研究を推進すれば、いずれADと差別化できる候補因子を見出せる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 9 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) Funded Workshop (1 results)

  • [Int'l Joint Research] Cardiff University(英国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Cardiff University/the Systems Immunity Research Institute(英国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Beta-Amyloid Increases the Expression Levels of Tid1 Responsible for Neuronal Cell Death and Amyloid Beta Production.2020

    • Author(s)
      Zhou C, Taslima F, Abdelhamid M, Kim SW, Akatsu H, Michikawa M, Jung CG.
    • Journal Title

      Mol Neurobiol.

      Volume: Feb;57(2): Issue: 2 Pages: 1099-1114

    • DOI

      10.1007/s12035-019-01807-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comprehensive quantification of purine and pyrimidine metabolism in Alzheimer's disease postmortem cerebrospinal fluid by LC?MS/MS with metal‐free column2020

    • Author(s)
      Muguruma Yoshio、Tsutsui Haruhito、Akatsu Hiroyasu、Inoue Koichi
    • Journal Title

      Biomedical Chromatography

      Volume: 34 Issue: 2

    • DOI

      10.1002/bmc.4722

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flotillin is a Novel Diagnostic Blood Marker of Alzheimer's Disease.2019

    • Author(s)
      Abdullah M, Kimura N, Akatsu H, Hashizume Y, Ferdous T, Tachita T, Iida S, Zou K, Matsubara E, Michikawa M.
    • Journal Title

      J Alzheimers Dis.

      Volume: 72 Issue: 4 Pages: 1165-1176

    • DOI

      10.3233/jad-190908

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differential protein expression of DARPP-32 versus Calcineurin in the prefrontal cortex and nucleus accumbens in schizophrenia and bipolar disorder2019

    • Author(s)
      Kunii Yasuto、Hino Mizuki、Matsumoto Junya、Nagaoka Atsuko、Nawa Hiroyuki、Kakita Akiyoshi、Akatsu Hiroyasu、Hashizume Yoshio、Yabe Hirooki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 14877-14877

    • DOI

      10.1038/s41598-019-51456-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] [Effects of drug treatment on the surviral-time in patients with dementia2019

    • Author(s)
      Manabe T, Mizukami K, Matsuoka T, Ogawa N, Kanesaka T, Taniguchi C, Yamamoto S, Hashizume Y, Ohara H, Yamamoto T, Akatsu H.
    • Journal Title

      Nihon Ronen Igakkai Zasshi

      Volume: 56(2) Pages: 171-180

    • NAID

      130007650185

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pneumonia-associated death in patients with dementia: A systematic review and meta-analysis2019

    • Author(s)
      Manabe Toshie、Fujikura Yuji、Mizukami Katsuyoshi、Akatsu Hiroyasu、Kudo Koichiro
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 3 Pages: e0213825-e0213825

    • DOI

      10.1371/journal.pone.0213825

    • NAID

      120007133511

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isotope Corrected Chiral and Achiral Nontargeted Metabolomics: An Approach for High Accuracy and Precision Metabolomics Based on Derivatization and Its Application to Cerebrospinal Fluid of Patients with Alzheimer's Disease.2019

    • Author(s)
      Takayama T, Mizuno H, Toyo'oka T, Akatsu H, Inoue K, Todoroki K.
    • Journal Title

      Anal Chem

      Volume: 19(3) Issue: 7 Pages: 4396-4404

    • DOI

      10.1021/acs.analchem.8b04852

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors influencing hospital admission among patients with autopsy-confirmed dementia.2019

    • Author(s)
      Matsuoka T, Manabe T, Akatsu H, Hashizume Y, Yamamoto S, Ogawa N, Kanesaka T, Taniguchi C, Yamamoto T, Mizukami K.
    • Journal Title

      Psychogeriatrics.

      Volume: 19(3) Issue: 3 Pages: 255-263

    • DOI

      10.1111/psyg.12393

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum levels of proteins involved in amyloid-β clearance are related to cognitive decline and neuroimaging changes in mild cognitive impairment.2019

    • Author(s)
      Liu S, Suzuki H, Ito H, Korenaga T, Akatsu H, Meno K, Uchida K.
    • Journal Title

      Alzheimers Dement (Amst).

      Volume: Jan 12 Issue: 1 Pages: 85-97

    • DOI

      10.1016/j.dadm.2018.11.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated analysis of human genetic association study and mouse transcriptome suggests LBH and SHF genes as novel susceptible genes for amyloid-β accumulation in Alzheimer's disease.2018

    • Author(s)
      Yamaguchi-Kabata Y, Morihara T, Ohara T, Ninomiya T, Takahashi A, Akatsu H, Hashizume Y, Hayashi N, Shigemizu D, Boroevich KA, Ikeda M, Kubo M, Takeda M, Tsunoda T.
    • Journal Title

      Hum Genet.

      Volume: 37(6-7) Issue: 6-7 Pages: 521-533

    • DOI

      10.1007/s00439-018-1906-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TAR DNA-Binding Protein 43 and Disrupted in Schizophrenia 1 Coaggregation Disrupts Dendritic Local Translation and Mental Function in Frontotemporal Lobar Degeneration.2018

    • Author(s)
      Endo R, Takashima N, Nekooki-Machida Y, Komi Y, Hui KK, Takao M, Akatsu H, Murayama S, Sawa A, Tanaka M.
    • Journal Title

      Biol Psychiatry.

      Volume: 84(7) Issue: 7 Pages: 509-521

    • DOI

      10.1016/j.biopsych.2018.03.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology2018

    • Author(s)
      Fujita Kyota、Chen Xigui、Homma Hidenori、Tagawa Kazuhiko、Amano Mutsuki、Saito Ayumu、Imoto Seiya、Akatsu Hiroyasu、Hashizume Yoshio、Kaibuchi Kozo、Miyano Satoru、Okazawa Hitoshi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 433-433

    • DOI

      10.1038/s41467-018-02821-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complement Activation in Capillary Cerebral Amyloid Angiopathy2017

    • Author(s)
      Matsuo Ko、Shindo Akihiro、Niwa Atsushi、Tabei Ken-ichi、Akatsu Hiroyasu、Hashizume Yoshio、Akiyama Haruhiko、Ayaki Takashi、Maki Takakuni、Sawamoto Nobukatsu、Takahashi Ryosuke、Oikawa Shinji、Tomimoto Hidekazu
    • Journal Title

      Dement Geriatr Cogn Disord

      Volume: 44 Issue: 5-6 Pages: 343-353

    • DOI

      10.1159/000486091

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome.2017

    • Author(s)
      Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome.
    • Journal Title

      Sci Rep.

      Volume: 7(1) Issue: 1 Pages: 15876-15876

    • DOI

      10.1038/s41598-017-16189-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative Analysis of Cortical Microinfarcts and Microbleeds using 3.0-Tesla Postmortem Magnetic Resonance Images and Histopathology.2017

    • Author(s)
      Niwa A, Ii Y, Shindo A, Matsuo K, Ishikawa H, Taniguchi A, Takase S, Maeda M, Sakuma H, Akatsu H, Hashizume Y, Tomimoto H.
    • Journal Title

      J Alzheimers Dis.

      Volume: 59 Issue: 3 Pages: 951-959

    • DOI

      10.3233/jad-161242

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia2017

    • Author(s)
      Manabe T, Mizukami K, Akatsu H, Hashizume Y, Ohkubo T, Kudo K, Hizawa N.
    • Journal Title

      Internal Medicine

      Volume: 56 Issue: 8 Pages: 907-914

    • DOI

      10.2169/internalmedicine.56.7879

    • NAID

      130006857581

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] How risky of intravenous iron administration?2019

    • Author(s)
      Hiroyasu Akatsu,Yoshihiro Kawade, et al
    • Organizer
      41th ESPEN(欧州静脈経腸栄養学会)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 地域在住高齢者の身体フレイルに及ぼす影響因子の検討2019

    • Author(s)
      赤津裕康、川出義弘 名古屋市立大学地域医療教育学 田中創始、荒川和幸、兼松孝好、大原弘隆 帝京大学医学部衛生学公衆衛生学講座 間辺利江、 足助病院  正木克由規、早川富博
    • Organizer
      第31回日本老年医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 15)神経病理学診断による認知症高齢者の生命予後期間に関するBPSDの影響について2019

    • Author(s)
      松岡珠美、間辺利江、赤津裕康、橋詰良夫、水上勝義
    • Organizer
      第31回日本老年医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 赤津裕康、川出義弘 名古屋市立大学地域医療教育学 田中創始、正木克由規、荒川和幸、兼松孝好、大原弘隆 名古屋市立大学医学部 成瀬兼人 帝京大学医学部衛生学公衆衛生学講座 間辺利江、 緑市民病院  山本憲一2019

    • Author(s)
      健康測定会がフレイルに及ぼす影響(身体無介入期間前後比較による行動変容)の検討
    • Organizer
      第31回日本老年医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 認知症の予防検証と薬物療法(薬剤選択)     ~名市大病院と名古屋市の取り組み~2019

    • Author(s)
      赤津裕康
    • Organizer
      第61回 全日本病院学会 in 愛知
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Fukushimura Brain Bank;Unique activity of Japanese private geriatric hospital2018

    • Author(s)
      Hiroyasu Akatsu 1,2), Norihiro Ogawa1), Takeshi Kanesaka1), Chie Taniguchi1), Sakon Yamamoto1), Takayuki Yamamoto, Masaki Takao, Shigeo Murayama, Yoshio Hashizume
    • Organizer
      ICN2018TOKYO 19th International Congress of Neuropathology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病患者試料の高精度キラルメタボロミクスによるマーカー探索2018

    • Author(s)
      高山卓大1,2・ 水野初1・ 豊岡利正1・ 赤津裕康3,4・ 井之上浩一5・ 轟木堅一郎1
    • Organizer
      日本質量分析学会・日本プロテオーム学会2018年合同大会
    • Related Report
      2018 Research-status Report
  • [Presentation] アルツハイマー型認知症の病理診断に基づく脳脊髄液・血液ペアのワイドターゲットメタボロミクス解析2018

    • Author(s)
      六車宜央, 筒井陽仁, 赤津裕康, 井之上浩一
    • Organizer
      第31回バイオメディカル分析科学シンポジウム 教育講演
    • Related Report
      2018 Research-status Report
  • [Presentation] 精神科病院からの紹介転院を契機に診断されたMM2-視床型孤発性クロイツフェルト・ヤコブ病の剖検例2018

    • Author(s)
      兼松孝好、林 紘太郎、荒川和幸、田中創始、赤津裕康、大原弘隆
    • Organizer
      第10回 日本神経病理学会 東海・北陸地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] 長期経静脈鉄剤投与剖検症例での肝臓鉄沈着、死後血液鉄関連因子の関連性の検討2018

    • Author(s)
      赤津裕康、川出義浩、間辺利江、井上風吹、井村尚斗、日比英志、荒川和幸、正木克由規、 田中創始、兼松孝好、橋詰良夫、常山幸一、大原弘隆
    • Organizer
      第42回 日本鉄バイオサイエンス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Investigation on the effect of aminolevulinic acid on intestinal environment of aging mice2017

    • Author(s)
      *Akatsu H, Arai S, Tanaka T, Kamiya A, Arakawa K, Masaki Y, Tanaka H, Kanematsu T, Ohara H, Inoue K, J.-Z. Xia, Maruyama M.
    • Organizer
      ESPEN(欧州静脈経腸栄養学会)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病モデルマウスにおける脳特異的タンパク質α1‐chimaerinの発現2017

    • Author(s)
      加藤智子、小西吉裕、下濱俊、BEACH T. G.、赤津裕康
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] MCIとアルツハイマー病の血液バイオマーカーとしての補体タンパク質プロファイル2017

    • Author(s)
      劉珊、鈴木秀昭、目野浩二、赤津裕康、松川則之
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ピコリルアミン誘導体化法による短鎖脂肪酸のLC‐ESI‐MS/MS分析法の開発:腸内細菌叢解析への応用2017

    • Author(s)
      長友涼介、岡田泰毅、筒井陽仁、赤津裕康
    • Organizer
      第30回バイオメディカル分析科学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 安定同位体誘導体化を基盤とする高精度キラルメタボロミクスの開発とアルツハイマー病患者CSF解析2017

    • Author(s)
      高山卓大、水野初、豊岡利正、井之上浩一、赤津裕康、轟木堅一郎
    • Organizer
      第30回バイオメディカル分析科学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Fmoc誘導体化LC‐MS/MSを用いたヒト脳脊髄液中のアミノ酸骨格代謝系の網羅的定量分析2017

    • Author(s)
      六車宜央、筒井陽仁、赤津裕康
    • Organizer
      第30回バイオメディカル分析科学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Remarks] Proffesor BP Morgan

    • URL

      https://www.cardiff.ac.uk/people/view/126579-morgan-paul

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 転倒予防システム2019

    • Inventor(s)
      赤津裕康、森啓悟、加藤周平
    • Industrial Property Rights Holder
      赤津裕康、森啓悟、加藤周平
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-117877
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] 国際アルツハイマー学会2017

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-02-22  

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