Elucidation of cognitive functions and molecular pathogenesis in Alzheimer's disease by CSF and PiB-PET

• Project/Area Number: 26461264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Gunma University
• Principal Investigator: Ikeda Masaki 群馬大学, 大学院医学系研究科, 准教授 (50222899)
• Co-Investigator(Kenkyū-buntansha): 池田 佳生 群馬大学, 大学院医学系研究科, 教授 (00282400) ; 山口 晴保 群馬大学, その他部局等, 名誉教授 (00158114) ; 牧岡 幸樹 群馬大学, 医学部附属病院, 助教 (10420176) ; 対馬 義人 群馬大学, 大学院医学系研究科, 教授 (20375546) ; 藤田 行雄 群馬大学, 医学部附属病院, 講師 (70420172) ; 山崎 恒夫 群馬大学, 大学院保健学研究科, 教授 (80200658) ; 古田 夏海 群馬大学, 医学部附属病院, 助教 (80625583) ; 平柳 公利 群馬大学, 医学部附属病院, 助教 (20701395) ; 長嶺 俊 群馬大学, 医学部附属病院, 助教 (20719918)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: アルツハイマー病 / 脳アミロイドβ / 大脳皮質微小出血 / PiB-PET / 脳脊髄液 / 脳血流SPECT / 進行性失語 / Amyloid β / microbleeds / CSF / アミロイドPET / 髄液 / アミロイドβ / タウ / βアミロイド / 原発性進行性失語症 / 後部脳萎縮症

Outline of Final Research Achievements

All four clinical subtypes of AD significantly increased CSF ptau-181 and decrease of Aβ1-42 compared with non-demented subjects（p<0.0001）. In logopenic progressive aphasic AD (l-AD) patients group, the number of lobar cerebral microbleeds (LCMBs) significantly increased in the left hemisphere than right side, although visuospatial cognition deficit AD (v-AD) did not show such lateralities. Decreased cerebral blood flow (CBF) and glucose hypometabolism were observed in left side, which may lead to speech disturbance, especially logopenic progressive aphasia.

Research Products

• [Journal Article] An analysis of prognostic factors after percutaneous endoscopic gastronomy palcement in Japansese patients with amyotrophic lateral sclerosis (2017)
  • Author(s): Nagashima K, Furuta N, Makioka K, Fujita Y, Ikeda M, Ikeda Y
  • Journal Title: J Neurol Sci Volume: 376 Pages: 202-205
  • DOI: 10.1016/j.jns.2017.03.029
  • Peer Reviewed
• [Journal Article] Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease. (2016)
  • Author(s): K.Furukawa,N.Tomita,D.Uematsu, K. Okahara, H.Shimada,
  • Journal Title: Geriatr Gerontol Int. Volume: 印刷中 Issue: 2 Pages: 1-8
  • DOI: 10.1111/ggi.12696
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease. (2016)
  • Author(s): Makioka K, Yamazaki T, Takatama M, Ikeda M, Murayama S, Okamoto K, Ikeda Y.
  • Journal Title: J Neurol Sci Volume: 365 Pages: 101-107
  • DOI: 10.1016/j.jns.2016.03.035
  • Peer Reviewed
• [Journal Article] Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains. (2016)
  • Author(s): Nagamine S, Yamazaki T, Makioka K, Fujita Y, Ikeda M, Takatama M, Okamoto K, Yokoo H, Ikeda Y.
  • Journal Title: Neuropathology Volume: 36 Issue: 4 Pages: 333-345
  • DOI: 10.1111/neup.12277
  • Peer Reviewed
• [Journal Article] Anti-MuSK Antibody-positive Myasthenia Gravis Mimicking Amyotrophic Lateral Sclerosis (2015)
  • Author(s): Furuta N, Ishizawa K, Shibata M, Tsukagoshi S, Nagamine S, Makioka K, Fujita Y, Ikeda M, Yoshimura S, Motomura M, Okamoto K, Ikeda Y.
  • Journal Title: Internal Medicine Volume: 54 Issue: 19 Pages: 2497-2501
  • DOI: 10.2169/internalmedicine.54.4645
  • NAID: 130005101803
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] SF levels of Aβ1-38/Aβ1-40/Aβ1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease. (2014)
  • Author(s): Ikeda M, Tashiro Y, Takai E, Kurose S, Fugami N, Tsuda K, Arisaka Y, KodairaS, Fujita Y, Makioka K, Mizuno Y, Shimada H, Harigaya Y, Takatama M, Amari M, Yamazaki T,Yamaguchi H, Higuchi T, Okamoto K, Tsushima Y, Ikeda Y.
  • Journal Title: Amyloid Volume: 21 Issue: 4 Pages: 238-245
  • DOI: 10.3109/13506129.2014.949231
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunolocalization of Smurf1 in Hirano bodies. (2014)
  • Author(s): Makioka K, Yamazaki T, Takatama M, Ikeda M, Okamoto K
  • Journal Title: J Neurol Sci Volume: 336 Issue: 1-2 Pages: 24-28
  • DOI: 10.1016/j.jns.2013.09.028
  • Peer Reviewed / Open Access
• [Journal Article] Lack of genetic association between TREM2 and late-onset Alzheimer’s disease in a Japanese population (2014)
  • Author(s): Akinori Miyashitaa, Yanan Wen 他
  • Journal Title: J Alzheimer's Dis. Volume: 印刷中 Issue: 4 Pages: 1301-1308
  • DOI: 10.3233/jad-140225
  • Peer Reviewed / Open Access
• [Journal Article] Dominantly Inherited Alzheimer’s Network (DIAN) 研究について (2014)
  • Author(s): 森 啓，東海林幹夫，池田将樹，池内 健，岩坪 威，嶋田裕之
  • Journal Title: Dementia Japan Volume: 28 Pages: 116-126
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Analysis of microbleeds in clinical variants of AD on CSF and Neuroimaging markers. (2017)
  • Author(s): Ikeda M, Tashiro Y, Makioka K, Kasahara H, Fujita Y, Nagashima K, Hirayanagi K, Nagamine S, Furuta N, Amari M, Takatama M, Okamoto K, Yamazaki T, Yamaguchi H, Higuchi T, Tsushima Y, Ikeda Y.
  • Organizer: AAIC2016
  • Place of Presentation: トロント（カナダ）
  • Year and Date: 2017-07-25
  • Int'l Joint Research
• [Presentation] Microbleeds in clinical subtypes of AD on CSF and Neuroimaging markers. (2017)
  • Author(s): Ikeda M, Tashiro Y, Makioka K, Kasahara H, Fujita Y, Nagashima K, Hirayanagi K, Nagamine S, Furuta N, Tsukagoshi S, Sekine A, Furuta M, Amari M, Okamoto K, Takatama M, Yamazaki T, Yamaguchi H, Higuchi T, Tsushima Y, Ikeda Y.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸
  • Year and Date: 2017-05-20
• [Presentation] 脳アミロイドアンギオパチー関連小血管病変とアルツハイマー病． (2017)
  • Author(s): 池田将樹
  • Organizer: 第42回日本脳卒中学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2017-03-16
  • Invited
• [Presentation] 脳表ヘモジデリン沈着を呈するADにおけるCSFマーカーと脳画像の臨床的検討． (2016)
  • Author(s): 池田将樹，笠原浩生，牧岡幸樹，池田佳生．
  • Organizer: 第35回日本認知症学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-02
• [Presentation] 脳表ヘモジデリン沈着を認めるADにおけるCSFマーカーと脳画像の検討． (2016)
  • Author(s): 池田将樹，笠原浩生，牧岡幸樹，池田佳生．
  • Organizer: 第7回日本脳血管・認知症学会総会Vas-Cog Japan2016
  • Place of Presentation: 金沢
  • Year and Date: 2016-08-06
• [Presentation] 認知症の急速な悪化を認め，約1年の経過で死亡したクロツフェルト・ヤコブの1例． (2015)
  • Author(s): 田中志子，池田将樹，高尾昌樹，美原 盤，北本哲之，佐藤克也，池田佳生．
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: 青森
  • Year and Date: 2015-10-03
• [Presentation] PES症候群を呈しMAPT遺伝子異常を認めたFTDP-17の1例． (2015)
  • Author(s): 浦 茂久，長沼亮滋，黒島研美，吉田一人，大槻美佳，池田将樹，矢部一郎，佐々木秀直．
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: 青森
  • Year and Date: 2015-10-03
• [Presentation] ADの臨床病型におけるmicrobleedsとCSFおよびPiB-PET/神経画像の検討． (2015)
  • Author(s): 池田将樹，甘利雅邦，高玉真光，岡本幸市，山崎恒夫，山口晴保，樋口徹也，対馬義人，池田佳生．
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: 青森
  • Year and Date: 2015-10-02
• [Presentation] Analysis of microbleeds in clinical variants of AD on CSF and Neuroimaging markers. (2015)
  • Author(s): Ikeda M, Tashiro Y, Makioka K, Kasahara H, Fujita Y, Nagashima K, Hirayanagi K, Nagamine S, Furuta N, Amari M, Takatama M, Okamoto K, Yamazaki T, Yamaguchi H, Higuchi T, Tsushima Y, Ikeda Y.
  • Organizer: VAS-COG 2015 TOKYO
  • Place of Presentation: TOKYO
  • Year and Date: 2015-09-18
  • Int'l Joint Research
• [Presentation] Early-onset Alzheimer’s disease, dementia with Lewy bodies and posterior cortical atrophy in cognitive deficits, CSF and 11C PiB-PET. (2015)
  • Author(s): Ikeda M, Tashiro Y, Arai K, Amari M, Takatama M, Harigaya Y, Okamoto K, Yamazaki T, Yamaguchi H, Higuchi T, Tsushima Y, Yoshio Ikeda.
  • Organizer: AAIC2015
  • Place of Presentation: Washington D.C.
  • Year and Date: 2015-07-20
  • Int'l Joint Research
• [Presentation] Relationship between diabetes mellitus and 11C PiB-PET in Alzheimer’s disease. (2015)
  • Author(s): Ikeda M, Fujita Y, Nagashima K, Makioka K, Nagamine S, Furuta N, Hirayanagi K, Tsugashi S，Kasahara H, Higuchi T, Tsushima Y, Yoshio Ikeda.
  • Organizer: ICME2015
  • Place of Presentation: Okayama, Japan
  • Year and Date: 2015-06-20
  • Int'l Joint Research
• [Presentation] 原発性進行性失語症の髄液マーカー/画像解析と言語・認知機能、リハビリ効果の検討． (2015)
  • Author(s): 池田将樹，田代裕一，甘利雅邦，和田直樹，白倉賢二，山崎恒夫，山口晴保．
  • Organizer: 第52回日本リハビリテーション医学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-30
• [Presentation] 当院Stroke Care Unitで認められたpusher現象の臨床的検討 (2015)
  • Author(s): 和田直樹，田澤昌之，伊部洋子，黒崎みのり，池田将樹，白倉賢二．
  • Organizer: 第52回日本リハビリテーション医学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-30
• [Presentation] PCAを呈するAD，早期発症型AD，DLBの臨床，髄液および画像的検討. (2015)
  • Author(s): 池田将樹, 田代裕一, 田代裕一，甘利雅邦，高玉真光, 岡本幸市, 針谷康夫，山崎恒夫，山口晴保，樋口徹也，対馬義人, 池田佳生．
  • Organizer: 第56回日本神経学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-23
• [Presentation] PCAを呈するAD，早期発症型AD，DLBの臨床および画像的検討 (2014)
  • Author(s): 池田将樹、田代裕一、甘利雅邦、高玉真光、岡本幸市、山崎恒夫、山口晴保、樋口徹也2、対馬義人、池田佳生
  • Organizer: 第33回日本認知症学会学術大会
  • Place of Presentation: 第33回日本認知症学会学術大会
  • Year and Date: 2014-12-01
• [Presentation] osterior cortical atrophyを呈したアルツハイマー病患者の画像的検討 (2014)
  • Author(s): 池田将樹, 田代裕一，藤田行雄，牧岡幸樹，甘利雅邦，高玉真光，岡本幸市，山崎恒夫，山口晴保，池田佳生
  • Organizer: 第20回日本脳循環代謝学会総会
  • Place of Presentation: 第20回日本脳循環代謝学会総会
  • Year and Date: 2014-11-21
• [Presentation] 原発性進行性失語症の言語・認知機能および神経放射線学的検討 (2014)
  • Author(s): 池田将樹、田代裕一、甘利雅邦、高玉真光、岡本幸市、山崎恒夫、山口晴保、樋口徹也、対馬義人、池田佳生
  • Organizer: 第5回日本血管認知症研究会（Vas-Cog2014）
  • Place of Presentation: メルパルク京都（京都）
  • Year and Date: 2014-08-23
• [Presentation] Analysis of cognitive functions, CSF biomarkers and Neuroimaging in posterior cortical atrophy and Alzheimer’s disease (2014)
  • Author(s): Masaki Ikeda,Yuichi Tashiro, Kunihiko Araki, Sachiko Kurose, Eriko Takai, Naoko Fugami, Kazuhisa Tsuda,Hirotaka Shimada, Masakuni Amari,Yasuo Harigaya,Masamitsu Takatama,Tsuneo Yamazaki, Haruyasu Yamaguchi, Koichi Okamoto, Tetsuya Higuchi, Yoshihito Tsushima,Yoshio Ikeda
  • Organizer: AAIC14 (Alzheimer’s Association International Conference)
  • Place of Presentation: Bella Sky Hall (Copenhagen, Denmark)
  • Year and Date: 2014-07-14
• [Presentation] posterior cortical atrophyを呈したアルツハイマー病症例の検討 (2014)
  • Author(s): 池田将樹，田代裕一，白倉賢二，山崎恒夫，山口晴保
  • Organizer: 第51回日本リハビリテーション医学会学術集会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2014-06-05
• [Presentation] Posterior cortical atrophyを呈したアルツハイマー病患者の11C PiB-PETと髄液の検討 (2014)
  • Author(s): 池田将樹、田代裕一， 荒木邦彦， 黒瀬佐知子， 高井恵理子， 普神直子， 津田和寿， 嶋田博孝， 岡本幸市， 樋口徹也， 池田佳生，対馬義人
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2014-05-24
• [Book] 認知症の診療治療最前線「健康長寿国での医療と周術期管理」 (2016)
  • Author(s): 池田将樹，池田佳生
  • Publisher: 真興交易株式会社医書出版部
• [Book] 運動機能障害：不随意運動「看護学生のための神経内科学」 (2015)
  • Author(s): 池田将樹，平田幸一編著
  • Publisher: 中外医学社
• [Book] 認知症とうつ・せん妄の鑑別診断ポイント「内科医が知っておくべき認知症・せん妄・うつの特徴と鑑別」 (2015)
  • Author(s): 池田将樹，池田佳生，企画：阿部康二
  • Publisher: メジカルビュー社