Anti-inflammatory effects on amyloid vaccination therapy by NSAID : a development of Alzheimer disease therapy

• Project/Area Number: 20591406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: MORIHARA Takashi Osaka University, 医学系研究科, 助教 (90403196)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Masatoshi 大阪大学, 医学系研究科, 教授 (00179649) ; KUDO Takashi 大阪大学, 医学系研究科, 准教授 (10273632) ; TANAKA Toshihisa 大阪大学, 医学系研究科, 講師 (10294068)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アルツハイマー病 / NSAID / 遺伝子 / アミロイドβ蛋白 / モデル動物 / 非ステロイド性抗炎症剤(NSAID) / イブプロフェン / APPトランスジェニックマウス / マイクログリア / 高感度CRP

Research Abstract

The suppression of Abea42 production by modified NSAIDs was not observed. APP Tg mice with mixed genetic background was reliable tool for the screening of the genes which modify the Abeta accumulation in brain. Candidate gene approaches have shown that no inflammation related gene associated with Abeta accumulation in our mice. CRP levels in elderly persons did not associate with the cognitive decline.

Research Products

• [Journal Article] 認知症の遺伝学 (2011)
  • Author(s): 森原剛史
  • Journal Title: Psychiatry Today 第27号 Pages: 13-15
• [Journal Article] Association between CAG repeat length in the PPP2R2B gene and Alzheimer disease in the Japanese population. (2011)
  • Author(s): Kimura R, Morihara T, Kudo T, Kamino K, Takeda M
  • Journal Title: Neurosci Lett. 487(3) Pages: 354-7
  • Peer Reviewed
• [Journal Article] KIBRA Genetic Polymorphism Influences Episodic Memory in Alzheimer's Disease, but Does Not Show Association with Disease in a Japanese Cohort. (2010)
  • Author(s): Hayashi N, Kazui H, Kamino K, Tokunaga H, Takaya M, Yokokoji M, Kimura R, Kito Y, Wada T, Nomura K, Sugiyama H, Yamamoto D, Yoshida T, Currais A, Soriano S, Hamasaki T, Yamamoto M, Yasuda Y, Hashimoto R, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T, Morihara T, Takeda M
  • Journal Title: Dement Geriatr Cogn Disord. 25;30(4) Pages: 302-308
  • Peer Reviewed
• [Journal Article] アルツハイマー病と遺伝要因 (2010)
  • Author(s): 森原剛史, 林紀行, 横小路美貴子, 武田雅俊
  • Journal Title: 老年精神医学雑誌 第21巻,第11号 Pages: 1264-1269
• [Journal Article] Association between CAG repeat length in the PPP2R2B gene and Alzheimer disease in the Japanese population. (2010)
  • Author(s): Kimura R, Morihara T, Kudo T, Kamino K, Takeda M.
  • Journal Title: Neurosci Lett. Volume: 487 Pages: 354-357
  • Peer Reviewed
• [Journal Article] KIBRA Genetic Polymorphism Influences Episodic Memory in Alzheimer's Disease, but Does Not Show Association with Disease in a Japanese Cohort. (2010)
  • Author(s): Hayashi N, Kazui H, Kamino K, Tokunaga H, Takaya M, Yokokoji M, Kimura R, Kito Y, Wada T, Nomura K, Sugiyama H, Yamamoto D, Yoshida T, Currais A, Soriano S, Hamasaki T, Yamamoto M, Yasuda Y, Hashimoto R, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T, Morihara T, Takeda M.
  • Journal Title: Dement Geriatr Cogn Disord. Volume: 30 Pages: 302-308
  • Peer Reviewed
• [Journal Article] Association study of KIBRA gene with memory performance in a Japanese population. (2010)
  • Author(s): Yasuda Y, Hashimoto R, Ohi K, Fukumoto M, Takamura H, Iike N, Yoshida T, Hayashi N, Takahashi H, Yamamori H, Morihara T, Tagami S, Okochi M, Tanaka T, Kudo T, Kamino K, Ishii R, Iwase M, Kazui H, Takeda M
  • Journal Title: World J Biol Psychiatry Volume: 11 Pages: 852-857
  • Peer Reviewed
• [Journal Article] The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system. (2009)
  • Author(s): Yanagida K, Okochi M, Tagami S, Nakayama T, Kodama TS, Nishitomi K, Jiang J, Mori K, Tatsumi S, Arai T, Ikeuchi T, Kasuga K, Tokuda T, Kondo M, Ikeda M, Deguchi K, Kazui H, Tanaka T, Morihara T, Hashimoto R, Kudo T, Steiner H, Haass C, Tsuchiya K, Akiyama H, Kuwano R, Takeda M
  • Journal Title: EMBO Mol Med 1(4) Pages: 223-35
  • Peer Reviewed
• [Journal Article] SORL1 is genetically associated with Alzheimer disease in a Japanese population. (2009)
  • Author(s): Kimura R, Yamamoto M, Morihara T, Akatsu H, Kudo T, Kamino K, Takeda M
  • Journal Title: Neurosci Lett. 18;461(2) Pages: 177-80
  • Peer Reviewed
• [Journal Article] Decrease of dynamin 2 levels in late-onset Alzheimer's disease alters Abeta metabolism. (2009)
  • Author(s): Kamagata E, Kudo T, Kimura R, Tanimukai H, Morihara T, Sadik MG, Kamino K, Takeda M
  • Journal Title: Biochem Biophys Res Commun. 13;379(3) Pages: 691-5
  • Peer Reviewed
• [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein : implications for the mechanism of tau aggregation. (2009)
  • Author(s): Sadik G, Tanaka T, Kato K, Yamamori H, Nessa BN, Morihara T, Takeda M
  • Journal Title: J Neurochem. 108(1) Pages: 33-43
  • Peer Reviewed
• [Journal Article] 初老期発症と高齢発症アルツハイマー病の異同:分子生物学の立場から (2009)
  • Author(s): 森原剛史, 武田雅俊
  • Journal Title: Cognition and Dementia 第8巻,第2号 Pages: 134-137
• [Journal Article] APP Tgマウスを用いたアルツハイマー病治療戦略にかかわる研究 (2009)
  • Author(s): 森原剛史
  • Journal Title: 神経化学 48巻,第1号 Pages: 23-28
  • NAID: 10025350268
• [Journal Article] Alzheimer病の遺伝子研究これまでの成果とこれからの課題 (2009)
  • Author(s): 森原剛史, 武田雅俊
  • Journal Title: 医学の歩み 第229巻,第3号 Pages: 205-210
• [Journal Article] 心理社会的問題と神経心理学的研究 (2009)
  • Author(s): 森原剛史
  • Journal Title: Psychiatry Today Medical Front International Limited 第21号 Pages: 28-29
• [Journal Article] アルツハイマー病の遺伝子研究 (2009)
  • Author(s): 森原剛史, 林紀行, 横小路美貴子, 数井裕光, 紙野晃人, 武田雅俊
  • Journal Title: 臨床精神医学 第38巻,第8号 Pages: 1007-1014
• [Journal Article] The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system (2009)
  • Author(s): Yanagida K, Okochi M, Tagami S, Nakayama T, Kodama TS, Nishitomi K, Jiang J, Mori K, Tatsumi S, Arai T, Ikeuchi T, Kasuga K, Tokuda T, Kondo M, et al
  • Journal Title: EMBO Mol Med Jul ; 1(4) Pages: 223-35
  • Peer Reviewed
• [Journal Article] Destruxin E decreases Beta-amyloid generation by reducing colocalization of beta-amyloid-cleaving enzyme 1 and beta-amyloid protein precursor (2009)
  • Author(s): Itoh N, Okochi M, Tagami S, Nishitomi K, Nakayama T, Yanagida K, Fukumori A, Jiang J, Mori K, Hosono M, Kikuchi J, Nakano Y, Takinami Y, Dohi K, Nishigaki A, Takemoto H, et al
  • Journal Title: Neurodegener Dis. 6(5-6) Pages: 230-9
  • Peer Reviewed
• [Journal Article] TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function (2009)
  • Author(s): Ohi K, Hashimoto R, Yasuda Y, Kiribayashi M, Iike N, Yoshida T, Azechi M, Ikezawa K, Takahashi H, Morihara T, et al
  • Journal Title: Genes Brain Behav Jun ; 8(4) Pages: 473-80
  • Peer Reviewed
• [Journal Article] SORL1 is genetically associated with Alzheimer disease in a Japanese population (2009)
  • Author(s): Kimura R, Yamamoto M, Morihara T, Akatsu H, Kudo T, Kamino K, Takeda M.
  • Journal Title: Neurosci Lett 461(2) Pages: 177-80
  • Peer Reviewed
• [Journal Article] Decrease of dynamin 2 levels in late-onset Alzheimer's disease alters Abeta metabolism (2009)
  • Author(s): Kamagata E, Kudo T, Kimura R, Tanimukai H, Morihara T, Sadik MG, Kamino K, Takeda M.
  • Journal Title: Biochem Biophys Res Commun 379(3) Pages: 691-5
  • Peer Reviewed
• [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein : implications for the mechanism of tau aggregation (2009)
  • Author(s): Sadik G, Tanaka T, Kato K, Yamamori H, Nessa BN, Morihara T, Takeda M.
  • Journal Title: J Neurochem 108(1) Pages: 33-43
  • Peer Reviewed
• [Journal Article] Decrease of dynamin 2 levels in late-onset Alzheimer's diseasealters Abeta metabolism. (2009)
  • Author(s): Kamagata E, Kudo T, KimuraR, Tanimukai H, Morihara T, Sadik MG, Kamino K, TakedaM.
  • Journal Title: Biochem Biophys Ees Commun. Jan 4(Epub aheadof print)
  • Peer Reviewed
• [Journal Article] Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. (2008)
  • Author(s): Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA.
  • Journal Title: J Pharmacol Exp Ther. 326(1) Pages: 196-208
  • Peer Reviewed
• [Journal Article] Mild cognitive impairment and subjective cognitive impairment. (2008)
  • Author(s): Takeda M, Morihara T, Okochi M, Sadic G, Tanaka T.
  • Journal Title: Psychogeriatrics 8(4) Pages: 155-60
  • NAID: 10027274677
  • Peer Reviewed
• [Journal Article] Processes of beta-amyloid and intracellular cytoplasmic domain generation by presenilin/gamma-secretase. (2008)
  • Author(s): Tagami S, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M
  • Journal Title: Neurodegener Dis. 5(3-4) Pages: 160-2
  • Peer Reviewed
• [Journal Article] Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers. (2008)
  • Author(s): Aidaralieva NJ, Kamino K, Kimura R, Yamamoto M, Morihara T, Kazui H, Hashimoto R, Tanaka T, Kudo T, Kida T, Okuda J, Uema T, Yamagata H, Miki T, Akatsu H, Kosaka K, Takeda M
  • Journal Title: J Hum Genet 53(4) Pages: 296-302
  • Peer Reviewed
• [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with14-3-3 protein : implications for the mechanism of tau aggregation. (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yamamori H, Nessa BN, Morihara T, Takeda M.
  • Journal Title: J Neurochem Jan ; 108(1) Pages: 33-43
  • Peer Reviewed
• [Journal Article] Difficulty identifying spinocerebellar ataxia 17 from precedingpsychiatric symptoms. (2008)
  • Author(s): Ohi K, Hashimoto R, Sugai F, Yasuda Y, Tagami s, Takamura H, Morihara T, Okochi M, Tanaka T, Kudo T, Sakoda s, Takeda M.
  • Journal Title: Psychiatry Clin Neurosci 62(5) Pages: 625-625
  • Peer Reviewed
• [Journal Article] Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia. (2008)
  • Author(s): Takahashi H, Iwase M, Ishii R, Ohi K, Fukumoto M, Azechi M, Ikezawa K, Kurimoto R, CanuetL, Nakahachi T, like N, TagamiS, Morihara T, Okochi M, TanakaT, Kazui H, Yoshida T, Tanimukai H, Yasuda Y, Kudo T, Hashimoto R, Takeda M.
  • Journal Title: Neurosci Res Nov ; 62(3) Pages: 187-94
  • Peer Reviewed
• [Journal Article] Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. (2008)
  • Author(s): Begum AN, Jones MR, Iim GP, MoriharaT, Kim P, Heath DD, Eock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA
  • Journal Title: J Pharmacol Exp Ther Jul ; 326(l) Pages: 196-208
  • Peer Reviewed
• [Journal Article] Processes of beta-amyloid and intracellular cytoplasmic domaingeneration by presenilin/gamma-secretase. (2008)
  • Author(s): Tagami s, Okochi M, FukumoriA, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M.
  • Journal Title: Neurodegener Dis. 5(3-4) Pages: 160-2
  • Peer Reviewed
• [Journal Article] Dynamin 2 gene is a novel susceptibility gene for late-onsetAlzheimer disease in non-APOE-epsilon4 carriers (2008)
  • Author(s): Aidaralieva NJ, Kamino K, Kimura R, Yamamoto M, Morihara T, Kazui H, Hashimoto R, Tanaka T, Kudo T, Kida T, Okuda J, Uema T, Yamagata H, Miki T, Akatsu H, Kosaka K, Takeda M.
  • Journal Title: J Hum Genet. 53(4) Pages: 296-302
  • Peer Reviewed
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precisionof S3 cleavage of Notch-1. (2008)
  • Author(s): Tagami s, Okochi M, YanagidaK, Ikuta A, Fukumori A, Matsumoto N, Ishizuka-KatsuraY, Nakayama T, Itoh N, Jiang J, Nishitomi K, Kamino K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Chiba s, Takeda M.
  • Journal Title: Mol Cell Biol 28(1) Pages: 165-76
  • Peer Reviewed
• [Journal Article] A molecular chaperone inducer protects neurons from ER stress. (2008)
  • Author(s): Kudo T, Kanemoto S, Hara H, Morimoto N, Morihara T, Eimura R, Tabira T, Imaizumi K, Takeda M.
  • Journal Title: Cell Death Differ 15(2) Pages: 364-75
  • Peer Reviewed
• [Presentation] Identification of a gene which controls Aβ accumulation using APP Tg mice with mixed genetic background (2010)
  • Author(s): Takashi MORIHARA, Noriyuki HAYASHI, Mikiko YOKOKOJI, Hiroyasu Akatsu, Eriko Fukusho, Hiroaki Kazui, Hitoshi TANIMUKAI, Shinji TAGAMI, Masayasu Okochi, Toshihisa TANAKA, Takashi KUDO, Masatoshi Takeda
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease (ICAD)
  • Place of Presentation: Honolulu, USA
• [Presentation] アルツハイマー病予防の可能性:抗炎症剤を中心に (2009)
  • Author(s): 森原剛史
  • Organizer: 第16回日本未病システム学会認知症の未病シンポジウム
  • Place of Presentation: 大阪
• [Presentation] Genetic Study on Alzheimer Disease (2009)
  • Author(s): 森原剛史
  • Organizer: 2009International Meeting of the International Psychogeriatric Association Symposist
  • Place of Presentation: Rio de Janeiro, Brazil
• [Presentation] Drastic Impact on Abeta Accumulation in APP Tg Mice By Genetic Background. (2008)
  • Author(s): MORIHARA T, YOKOKOJI M, HAYASHI N, Nosm E, MORIK, TAGAMI s, KUDO T, KAMINO K, TAKEDA M
  • Organizer: ICAD 2008
  • Place of Presentation: Chicago USA .
• [Presentation] Effects Of Learning Therapy On Elderly Japanese In Osaka : A Randomized Controlled Single-blind Multi-center Trial (2008)
  • Author(s): Noriyuiki Hayashi, Hiroaki Kazui, AyumiKono, Takashi Morihara, TakahiroHigashi, Yaeko Hata, Hiromi Yoshida, Kousuke Masuda, Naoya Kuwata, Masuhir)Okuda, Masatoshi Takeda
  • Organizer: Alzheimer's Association International Conferenceon Alzheimer's Disease (ICAD)
  • Place of Presentation: Chicago USA
• [Presentation] APP TgマウスのAβ蓄積量はマウス背景遺伝子の違いで大きく変わる (2008)
  • Author(s): 森原剛史, 横小路美貴子, 林紀行, 田上真次, 工藤喬, 熨斗英理子, 伊藤尚弘, 西富晃平, 武田雅俊
  • Organizer: 日本認知症学会2008
  • Place of Presentation: 前橋
• [Presentation] デイサービス施設での非薬物療法~認知トレーニング(計算・音読)と創作活動(図画・工作)による無作為割付単盲検多施設研究 (2008)
  • Author(s): 林紀行, 森原剛史, 数井裕光, 河野あゆみ, 奥田益弘, 畑八重子, 吉田浩美, 増田康介, 桑田直弥, 武田雅俊
  • Organizer: 日本認知症学会2008
  • Place of Presentation: 前橋
• [Presentation] アルツハイマー病モデルマウス(APP Tg)のアミロイド病理は背景遺伝子で大きく変わる。 (2008)
  • Author(s): 横小路美貴子, 森原剛史, 林紀行田上真次, 武田雅俊
  • Organizer: 第51回神経化学大会2008
  • Place of Presentation: 富山
• [Remarks] Medical Tribune 2009年12月17日 vol 42 No 51 page 36-37
• [Remarks] 日本未病システム学会認知症予防に関する知見への正確な確認を発症前からの投与が重要