• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Earliest detection of alpha-synuclein lesions for differential diagnosis

Research Project

Project/Area Number 25670427
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

FUMIMURA Yuichi  公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 研究員 (30647243)

Co-Investigator(Kenkyū-buntansha) 内原 俊記  公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 副参事研究員 (10223570)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsαシヌクレイン / パーキンソン病 / レヴィ小体型認知症 / MIBG心筋シンチグラフィー / レヴィー小体型認知症 / 高齢サル心筋 / レヴィ小体 / レヴィ小体病 / 心臓交感神経 / 神経突起病理学 / レヴィー小体 / レヴィー小体病 / MIBG 心筋シンチグラフィー
Outline of Final Research Achievements

We first demonstrated phosphorylated α-synuclein (pαsyn) aggregation in cardiac sympathetic nerves in the subendocardial area in the early stages of Lewy body disease (LBD) by using immunostained free-floating sections. Accumulation of pαsyn aggregates preceded the disappearance of tyrosine hydroxylase imunnoreactive axons. In LBD, pαsyn aggregation and distal-dominant degeneration of the cardiac sympathetic nervous system may represent the common pathological mechanism. We demonstrated a tight quantitative correlation between postmortem examination of remaining axons and premortem MIBG uptake in an autopsy series of patients with or without LBD. Sympathetic nervous system has distinguishable orientations. Therefore, the analyses of cardiac sympathetic nerve fibers have possibilities to reveal the earliest changes and pathological mechanism underlying a common degenerative process in LBD.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (12 results) (of which Invited: 4 results) Book (6 results) Remarks (2 results)

  • [Journal Article] An order in Lewy body disorders: Retrograde degeneration in hyperbranching axons as a fundamental structural template accounting for focal/multifocal Lewy body disease2017

    • Author(s)
      Uchihara T
    • Journal Title

      Neuroptahology

      Volume: 37 Issue: 2 Pages: 129-49

    • DOI

      10.1111/neup.12348

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Perirhinal accumulation of neuronal alpha-synuclein in a multiple system atrophy patient with dementia2017

    • Author(s)
      Saito M, Hara M, Ebashi M, Morita A, Okada K, Homma T, Sugitani M, Endo K, Uchihara T, Kamei S
    • Journal Title

      Neuropathology

      Volume: 33 Issue: 5 Pages: 431-440

    • DOI

      10.1111/neup.12381

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-repeat tau with grain-like structures and distribution in an 83-year-old man2017

    • Author(s)
      Kasahata N, Sato T, Onishi I, Kitagawa M, Uchihara T, Hirokawa K
    • Journal Title

      J Alzheimer Dis

      Volume: 53

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like2016

    • Author(s)
      Uchihara T, Endo K, Kondo H, Okabayashi S, Shimozawa N, Yasutomi Y, Adachi E, Kimura N
    • Journal Title

      Acta Neuropathol Comm

      Volume: 4 Issue: 1 Pages: 118-118

    • DOI

      10.1186/s40478-016-0385-5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis,2016

    • Author(s)
      Umahara T, Uchihara T, Shibata N, Nakamura A, Hanyu H
    • Journal Title

      Brain Res

      Volume: 1646 Pages: 132-8

    • DOI

      10.1016/j.brainres.2016.05.051

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies2016

    • Author(s)
      Uchihara T, Giasson B.
    • Journal Title

      Acta Neuropathol

      Volume: 131 Issue: 1 Pages: 49-73

    • DOI

      10.1007/s00401-015-1485-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Direct quantitative correlation between cardiac MIBG uptake and remaining axons in cardiac sympathethic nerve in Lewy body disease2015

    • Author(s)
      Makoto Takahashi, Masako Ikemura, Teruaki Oka, Toshiki Uchihara, Koichi Wakabayashi, Akiyoshi Kakita, Hitoshi Takahashi, Mari Yoshida, Shuta Toru, Takayoshi Kobayashi, Satoshi Orimo
    • Journal Title

      Journal of Neurology, Neurosurgery, and Psychiatry

      Volume: Online First Issue: 9 Pages: 939-44

    • DOI

      10.1136/jnnp-2015-310686

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] パーキンソン病の細胞病理と脳内外の拡がり2015

    • Author(s)
      文村 優一
    • Journal Title

      The Cell

      Volume: 47(1) Pages: 5-8

    • Related Report
      2014 Research-status Report
  • [Journal Article] パーキンソン病の始まりとひろがり(総論)2015

    • Author(s)
      内原 俊記
    • Journal Title

      The Cell

      Volume: 47(1) Pages: 2-4

    • Related Report
      2014 Research-status Report
  • [Journal Article] Ultrastructural differences in pretangles between Alzheimer disease and corticobasal degeneration revealed by comparative light and electron microscopy2014

    • Author(s)
      Shinsui Tatsumi, Toshiki Uchihara, Ikuko Aiba, Yasushi Iwasaki, Maya Mimuro, Ryosuke Takahashi, Mari Yoshida
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 2 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s40478-014-0161-3

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] How progressive supranuclear palsy (PSP) is mimicked and what is mimicking PSP? PSP-like features without PSP cytopathology in three cases of Alzheimer’s disease/Parkinson’s disease.2014

    • Author(s)
      Kasahata N, Hagiwara M, Kato H, Miyazawa Y, Kamei T, Makita Y, Uchihara T.
    • Journal Title

      J Alzheimers Dis

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] An 85-year old male with revodpa-responsive Parkinsonism followed by dementia and supranuclear ophthalmoplegia caused by Alzheimer pathology without Lewy bodies2014

    • Author(s)
      Kasahata, N. Hagiwara, M. Kato, H. Nakamura, A. Uchihara, T.
    • Journal Title

      J Alzheimers Dis

      Volume: 39 Issue: 3 Pages: 471-476

    • DOI

      10.3233/jad-131508

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lateralized Cortical Involvement and Contralateral Parkinsonism without Basal Ganglia Involvement in Two Autopsy Cases of Corticobasal Syndrome-Alzheimer's Disease2014

    • Author(s)
      Homma, T. Takubo, H. Takahashi, K. Matsubara, S. Takahashi, M. Funata, N. Mochizuki, Y. Mizutani, T. Komori, T. Uchihara, T.
    • Journal Title

      J Alzheimers Dis

      Volume: 40 Issue: 1 Pages: 51-5

    • DOI

      10.3233/jad-131676

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lewy pathology in an autopsy case of FTLD-MND with reduced cardiac MIBG uptake and depletion of cardiac sympathetic fibers.2013

    • Author(s)
      Nomoto N, Orimo S, Uchihara T, Takahashi K, Fujioka T
    • Journal Title

      Parkinsonism Relat Disord

      Volume: 19 Issue: 4 Pages: 472-473

    • DOI

      10.1016/j.parkreldis.2012.10.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Corticobasal syndromeの病理と臨床の乖離を攻略する2016

    • Author(s)
      内原俊記
    • Organizer
      第35回日本認知症学会学術集会シンポジウム21「Corticobasal syndrome; 基礎と臨床」
    • Place of Presentation
      東京国際フォーラム(東京都、千代田区)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 混沌のなかの秩序 レヴィー病変は分岐の豊富な軸索先端から逆行性に進展する2016

    • Author(s)
      内原俊記
    • Organizer
      第57回日本神経病理学会総会学術研究会 シンポジウム2 典型像と非典型像―隠れた本質を見抜くー
    • Place of Presentation
      ホテルニューキャッスル(青森県、青森市)
    • Year and Date
      2016-06-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 混沌のなかの秩序-突起からひろがる神経変性-2016

    • Author(s)
      内原俊記
    • Organizer
      京都府立医科大学特別講義(招待講演)
    • Place of Presentation
      京都府立医科大学基礎医学学舎(京都府、京都市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Probable DLBの臨床診断基準を満たしたPSPの1剖検例2016

    • Author(s)
      内原俊記
    • Organizer
      第1回パーキンソン症候群・認知症の臨床・病理フォーラム
    • Place of Presentation
      中野サンプラザ(東京都、中野区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 特異な異常行動を呈したレヴィ正体病の1例2015

    • Author(s)
      融衆多,文村優一,廣川勝昱,内原俊記,小林高義.
    • Organizer
      第56回日本神経病理学会総会学術研究会
    • Place of Presentation
      九州大学百年行動(福岡県福岡市)
    • Year and Date
      2015-06-03
    • Related Report
      2015 Research-status Report
  • [Presentation] Immunohistochemical study of the most distal axons of the cardiac sympathetic nerve in Parkinson’s disease2014

    • Author(s)
      Yuichi Fumimura, Toshiki Uchihara
    • Organizer
      18th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2014-06-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 心筋内軸索最末端に想定されるαシヌクレイン最早期病変の追跡2014

    • Author(s)
      文村優一, 内原俊記
    • Organizer
      第55回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京(会場:学術総合センター)
    • Year and Date
      2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 心筋内軸索最末端に想定されるαシヌクレイン最早期病変の追跡 第2報2014

    • Author(s)
      文村優一, 内原俊記
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡(会場:福岡国際会議場等)
    • Year and Date
      2014-05-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 心筋内軸索最末端に想定されるαシヌクレイン最早期病変の追跡

    • Author(s)
      文村優一、内原俊記
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 心筋内軸索最末端に想定されるαシヌクレイン最早期病変の追跡 第2報

    • Author(s)
      文村優一、内原俊記
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] 心筋内軸索最末端に想定されるαシヌクレイン最早期病変の追跡

    • Author(s)
      文村優一、内原俊記
    • Organizer
      第55回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Immunohistochemical study of the most distal axons of the cardiac sympathetic nerve in Parkinson’s disease

    • Author(s)
      Yuichi Fumimura, Toshiki Uchihara
    • Organizer
      The MDS 18th International Congress
    • Place of Presentation
      スウェーデン
    • Related Report
      2013 Research-status Report
  • [Book] Encyclopedia of neurological sciences, 2nd ed. Edition2014

    • Author(s)
      Uchihara T
    • Publisher
      Elsevier
    • Related Report
      2013 Research-status Report
  • [Book] Neuropathology2014

    • Author(s)
      Uchihara T, Yoshida M
    • Publisher
      Blackwell Science
    • Related Report
      2013 Research-status Report
  • [Book] 病理と臨床2014

    • Author(s)
      遠藤堅太郎, 植松未帆, 金澤俊郎, 中村綾子, 安達栄治郎, 市川眞澄, 内原俊記
    • Total Pages
      6
    • Publisher
      文光堂
    • Related Report
      2013 Research-status Report
  • [Book] Encyclopedia of metalloproteins2013

    • Author(s)
      Uchihara T
    • Total Pages
      8
    • Publisher
      Springer
    • Related Report
      2013 Research-status Report
  • [Book] BRAIN and NERVE: 神経研究の進歩2013

    • Author(s)
      内原俊記
    • Total Pages
      17
    • Publisher
      医学書院
    • Related Report
      2013 Research-status Report
  • [Book] BRAIN and NERVE: 神経研究の進歩2013

    • Author(s)
      野本信篤, 内原俊記, 織茂智之
    • Total Pages
      9
    • Publisher
      医学書院
    • Related Report
      2013 Research-status Report
  • [Remarks] 研究の課題 CHALLENGE

    • URL

      http://www.igakuken.or.jp/parkinson/uchihara/challenge.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 脳病理形態(内原)研究室

    • URL

      http://www.igakuken.or.jp/parkinson/index2.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi