Neuropathological analysis of multiple system atrophy with cognitive impairment

• Project/Area Number: 25430048
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Niigata University
• Principal Investigator: Tada Mari 新潟大学, 脳研究所, 助教 (30646394)
• Co-Investigator(Kenkyū-buntansha): SHIMOHATA Takayoshi 新潟大学, 脳研究所, 准教授 (60361911) ; NISHIZAWA Masatoyo 新潟大学, 脳研究所, 教授 (80198457) ; TAKAHASHI Hitoshi 新潟大学, 脳研究所, 教授 (90206839)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 多系統萎縮症 / 神経変性疾患 / 認知機能障害 / 神経病理学 / 臨床病理学的研究 / 病理学的定量解析 / 臨床研究 / 病理学的解析

Outline of Final Research Achievements

Among 49 pathologically proven multiple system atrophy (MSA) cases, 12 cases developed cognitive decline (CD) in their disease course. There was no significant difference of age between cases with or without CD. The disease duration of cases with CD was variable (3-19 years). 50 % of these cases survived over 10 years after the disease onset. Quantitative analyses revealed that the density of neurons in the caudate head, but not in the frontal cortex and putamen, was lower in cases with CD than in cases without CD. There was no difference in the density of neuron nor glia withα-synuclein inclusions between cases with and without CD. These results suggested that degeneration of the caudate head could result in the dysfunction of the cortico-basal ganglia loop and influence in cognitive decline in MSA cases with long disease duration.

Research Products

• [Journal Article] Expression of aquaporin 1 and aquaporin 4 in the temporal neocortex of patients with Parkinson's disease. (2016)
  • Author(s): Hoshi A, Tsunoda A, Tada M, Nishizawa M, Ugawa Y, Kakita A.
  • Journal Title: Brain Pathol. Volume: - Issue: 2 Pages: 160-168
  • DOI: 10.1111/bpa.12369
  • Peer Reviewed / Open Access
• [Journal Article] Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With Special Reference to Astrocytic Tau Pathology. (2016)
  • Author(s): Yokoyama Y, Toyoshima Y, Shiga A, Tada M, Kitamura H, Hasegawa K, Onodera O, Ikeuchi T, Someya T, Nishizawa M, Kakita A, Takahashi H.
  • Journal Title: Brain Pathol. Volume: 26 Issue: 2 Pages: 155-166
  • DOI: 10.1111/bpa.12265
  • Peer Reviewed
• [Journal Article] Na,K-ATPaseα3 is a death target of alzheimer patient amyloid-β assembly. (2015)
  • Author(s): Ohnishi T, ..., Matsui K, ..., Hoshi M （計35名, 記載欄不足）
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 Issue: 32 Pages: 4465-4474
  • DOI: 10.1073/pnas.1421182112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of sodium pyruvate on exercise intolerance and muscle weakness due to mitochondrial myopathy: a case report (2015)
  • Author(s): 黒羽 泰子, 他田 真理, 河内 泉, 西澤 正豊, 松原 奈絵, 小池 亮子
  • Journal Title: Rinsho Shinkeigaku Volume: 55 Issue: 6 Pages: 412-416
  • DOI: 10.5692/clinicalneurol.cn-000652
  • NAID: 130005083894
  • ISSN: 0009-918X, 1882-0654
  • Peer Reviewed
• [Journal Article] Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia. (2015)
  • Author(s): Takeuchi R, Toyoshima Y, Tada M, Tanaka H, Shimizu H, Shiga A, Miura T, Aoki K, Aikawa A, Ishizawa S, Ikeuchi T, Nishizawa M, Kakita A, Takahashi H.
  • Journal Title: Brain Pathology Volume: in press Issue: 1 Pages: 82-94
  • DOI: 10.1111/bpa.12262
  • Peer Reviewed
• [Journal Article] C9ORF72 repeat-associated non-ATG-translated polypeptides are distributed independently of TDP-43 in a Japanese patient with c9ALS (2014)
  • Author(s): Konno T ほか
  • Journal Title: Neuropathol Appl Neurobiol Volume: 40 Issue: 6 Pages: 783-788
  • DOI: 10.1111/nan.12157
  • Peer Reviewed / Open Access
• [Journal Article] Haploinsufficiency of CSF-1R and clinicopathological characterization in patients with HDLS. (2014)
  • Author(s): Konno T, Tada M, Tada M, Koyama A, Nozaki H, Harigaya Y, Nishimiya J, Matsunaga A, Yoshikura N, Ishihara K, Arakawa M, Isami A, Okazaki K, Yokoo H, Ihoh K, Yoneda M, Kawamura M, Inuzuka T, Takahashi H, Nishizawa M, Onodera O, Kakita A, Ikeuchi T
  • Journal Title: Neurology Volume: 82 Issue: 2 Pages: 139-148
  • DOI: 10.1212/wnl.0000000000000046
  • Peer Reviewed
• [Journal Article] Pathology and sensitivity of current clinical criteria in corticobasal syndrome. (2014)
  • Author(s): Ouchi H, Toyoshima Y, Tada M, Oyake M, Aida I, Tomita I, Satoh A, Tsujihata M, Takahashi H, Nishizawa M, Shimohata T.
  • Journal Title: Mov Disord Volume: 29 Issue: 2 Pages: 238-44
  • DOI: 10.1002/mds.25746
  • Peer Reviewed
• [Journal Article] Hereditary diffuse leukoencephalopathy with spheroids (HDLS): a review of the literature on its clinical characteristics and mutations in the colony-stimulating factor-1 receptor gene. (2014)
  • Author(s): Konno T, Tada M, Tada M, Nishizawa M, Ikeuchi T.
  • Journal Title: Brain Nerve Volume: 66 Pages: 581-90
  • NAID: 40020089061
  • Peer Reviewed
• [Journal Article] Early clinical features of patients with progressive supranuclear palsy with predominant cerebellar ataxia. (2013)
  • Author(s): Kanazawa M, Tada M, Onodera O, Takahashi H, Nishizawa M, Shimohata T.
  • Journal Title: Parkinsonism Relat Disord Volume: 19 Issue: 12 Pages: 1149-51
  • DOI: 10.1016/j.parkreldis.2013.07.019
  • Peer Reviewed
• [Journal Article] Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of Japanese patients with novel SCARB2 mutations. (2013)
  • Author(s): Fu YJ, Aida I, Tada M, Tada M, Toyoshima Y, Takeda S, Nakajima T, Naito H, Nishizawa M, Onodera O, Kakita A, Takahashi H.
  • Journal Title: Neuropathol Appl Neurobiol Volume: epub ahead of print Issue: 5 Pages: 551-563
  • DOI: 10.1111/nan.12057
  • Peer Reviewed
• [Presentation] 常染色体優性遺伝性と考えられ高齢発症の家族性パーキンソン病の１剖検 (2015)
  • Author(s): 他田真理，横関明男，木村正志，池内健，石川厚, 高橋均，柿田明美
  • Organizer: 第56回日本神経病理学会総会学術研究会
  • Place of Presentation: 九州大学医学部百年講堂 (福岡県福岡市）
  • Year and Date: 2015-06-03
• [Presentation] HDLS患者脳におけるミクログリアの形態学的異常： Microgliopathyとして (2015)
  • Author(s): 他田真理、高橋 均、柿田明美
  • Organizer: 第56回日本神経学会総会学術大会
  • Place of Presentation: 新潟朱鷺メッセ(新潟県新潟市）
  • Year and Date: 2015-05-20
• [Presentation] 神経軸索スフェロイドを伴う白質脳症HDLS：Microgliaの組織学的異常 (2014)
  • Author(s): 他田真理，今野卓哉，他田正義，岡崎健一，荒川武蔵，横尾英明，山本 徹，伊東恭子，吉倉延亮，豊島靖子，小野寺理，西澤正豊，池内健, 高橋均，柿田明美
  • Organizer: 第５５回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京都千代田区一ツ橋 学術総合センター
  • Year and Date: 2014-06-05 – 2014-06-07
• [Presentation] 神経軸索スフェロイドを伴う白質脳症HDLS：Microgliaの組織学的異常 (2014)
  • Author(s): 他田真理，今野卓哉，他田正義，岡崎健一，荒川武蔵，横尾英明，山本 徹，伊東恭子，吉倉延亮，豊島靖子，小野寺理，西澤正豊，池内健, 高橋均，柿田明美
  • Organizer: 第５５回日本神経学会学術総会
  • Place of Presentation: 福岡国際会議場・福岡サンパレス・福岡国際センター
  • Year and Date: 2014-05-21 – 2014-05-23
• [Presentation] Hereditary diffuse leukoencephalopathy with spheroids (HDLS): Histological features of microglia (2014)
  • Author(s): Mari Tada, Takuya Konno，Masayoshi Tada，Ken-ichi Okazaki，Musashi Arakawa，Kyoko Itoh，Toru Yamamoto, Hideaki Yokoo, Nobuaki Yoshikura，Kenji Ishihara, Yasuko Toyoshima, Osamu Onodera, Masatoyo Nishizawa, Takeshi Ikeuchi，Hitoshi Takahashi，Akiyoshi Kakita
  • Organizer: American Academy of Neurology Annual meeting 2014
  • Place of Presentation: Pennsylvania Convention Center in Philadelphia, PA, USA
  • Year and Date: 2014-04-26 – 2014-05-03
• [Presentation] 神経軸索スフェロイドを伴う白質脳症HDLS：Microgliaの組織学的解析 (2013)
  • Author(s): 他田真理，今野卓哉，他田正義，岡崎健一，荒川武蔵，横尾英明，伊東恭子，吉倉延亮，豊島靖子，小野寺理，西澤正豊，池内健, 高橋均，柿田明美
  • Organizer: 第５４回日本神経病理学会総会学術研究会
  • Place of Presentation: タワーホール船堀
• [Presentation] 神経軸索スフェロイドを伴う白質脳症HDLS：Microgliaの組織学的解析 (2013)
  • Author(s): 他田真理，今野卓哉，他田正義，岡崎健一，荒川武蔵，横尾英明，伊東恭子，吉倉延亮，豊島靖子，小野寺理，西澤正豊，池内健, 高橋均，柿田明美
  • Organizer: 第５４回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム