Development of risk assessment and prevention of cerebral amyloid angiopathy-related cerebral hemorrhages

• Project/Area Number: 20390242
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kanazawa University
• Principal Investigator: YAMADA Masahito 金沢大学, 医学系, 教授 (80191336)
• Co-Investigator(Kenkyū-buntansha): YOSHITA Mitsuhiro 金沢大学, 医学系, 協力研究員 (60361995) ; 内木 宏延 福井大学, 医学部, 教授 (10227704)
• Co-Investigator(Renkei-kenkyūsha): NAIKI Hironobu 福井大学, 医学部, 教授 (10227704)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 脳アミロイドアンギオパチー / アミロイド / 脳内出血 / MRI / PET / アミロイドβ蛋白 / 実験モデル / 天然フェノール化合物 / 脳画像 / 診断マーカー / 試験管内モデル / 動物モデル

Research Abstract

We investigated cerebral amyloid angiopathy(CAA) and CAA-related hemorrhages to develop methods of risk assessment and prevention. We propose a table of biomarkers and risk factors to predict future development of CAA-related hemorrhages and other disorders. We established an in vitro model of CAA. We revealed that natural phenolic compounds inhibited fibril formation and oligomerization of amyloidβ-protein(Aβ) in in vitro and in vivo models.

Research Products

• [Journal Article] Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site specific binding (2012)
  • Author(s): Ono K, Li L, Takamura Y, Yoshiike Y, Zhu L, Han F, Mao X, Ikeda T, Takasaki JI, Nishijo H, Takashima A, Teplow DB, Zagorski MG, Yamada M
  • Journal Title: J Biol Cbem Volume: (印刷中) Issue: 18 Pages: 14631-14643
  • DOI: 10.1074/jbc.m111.325456
  • Peer Reviewed
• [Journal Article] Multiple cerebral infarcts with a few vasculitic lesions in the chronic stage of cerebral amyloid angiopathy-related inflammation (2012)
  • Author(s): Sakai K, Hayashi S, Sanpei K, Yamada M, Takahashi H
  • Journal Title: Neuropathology Volume: (印刷中) Issue: 5 Pages: 551-556
  • DOI: 10.1111/j.1440-1789.2011.01283.x
  • Peer Reviewed
• [Journal Article] Cerebral amyloid angiopathy (2012)
  • Author(s): Yamada M, Naiki H
  • Journal Title: Prog Mol Biol Transl Sci Volume: 107 Pages: 41-78
  • DOI: 10.1016/b978-0-12-385883-2.00006-0
  • NAID: 40016785952
  • ISBN: 9780123858832
  • Peer Reviewed
• [Journal Article] Predicting cerebral amyloid angiopathy-realated intracerebral hemorrhages and other cerebrovascular disorders in Alzheimer's disease (2012)
  • Author(s): Yamada M
  • Journal Title: Front Neurol Volume: 3 Pages: 1-8
  • DOI: 10.3389/fneur.2012.00064
  • Peer Reviewed
• [Journal Article] Effects of sex hormones on Alzheimer disease-associatedβ-amyloid oligomer formation in vitro (2011)
  • Author(s): Morinaga A, Ono K, Takasaki J, Ikeda T, Hirohata M, Yamada M
  • Journal Title: Exp Neurol Volume: 228 Pages: 298-302
  • Peer Reviewed
• [Journal Article] Vitamin A has antioligomerization effects on amyloidβ-protein in vitro (2011)
  • Author(s): Takasaki J-I, Ono K, Yoshiike Y, Hirohata M, Ikeda T, Morinaga A, Takashima A, Yamada M
  • Journal Title: J Alzheimers Dis Volume: 27 Pages: 271-280
  • Peer Reviewed
• [Journal Article] Vitamin A has antioligomerization effects on amyloid β-protein in vitro (2011)
  • Author(s): Takasaki J-I, Ono K, Yoshiike Y, Hirohata M, Ikeda T, Morinaga A, Takashima A, Yamada M
  • Journal Title: J Alzheimers Dis Volume: 27 Issue: 2 Pages: 271-280
  • DOI: 10.3233/jad-2011-110455
  • Peer Reviewed
• [Journal Article] 脳アミロイドアンギオパチーの病態 (2011)
  • Author(s): 山田正仁
  • Journal Title: 老年精神医学 Volume: 22 Pages: 72-77
• [Journal Article] 脳アミロイドアンギオパチーの疫学と臨床像 (2011)
  • Author(s): 廣畑美枝、山田正仁
  • Journal Title: 神経内科 Volume: 74 Pages: 472-478
• [Journal Article] 脳アミロイドアンギオパチーの臨床病理 (2011)
  • Author(s): 山田正仁
  • Journal Title: 臨床神経 Volume: 51 Pages: 1142-1142
• [Journal Article] Curcumin and Alzheimer's disease (2010)
  • Author(s): Hamaguchi T, Ono K, Yamada M
  • Journal Title: CNS Neurosci Ther Volume: 16 Pages: 285-297
  • Peer Reviewed
• [Journal Article] Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy (2010)
  • Author(s): Hirohata M, Yoshita M, Ishida C, Ikeda S-I, Tamaoka A, Kuzuhara S, Shoji M, Ando Y, Tokuda T, Yamada M
  • Journal Title: Eur J Neurol Volume: 17 Pages: 823-829
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid of Alzheimer patients promotes amyloidβ-protein oligomerization (2010)
  • Author(s): Ikeda T, Ono K, Elashoff D, Condron MM, Noguchi-Shinohara M, Yoshita M, Teplow DB, Yamada M
  • Journal Title: J Alzheimers Dis Volume: 21 Pages: 81-86
  • Peer Reviewed
• [Journal Article] Critical role of interfaces and agitation on the nucleation of Aβamyloid fibrils at low concentrations of Aβmonomers (2010)
  • Author(s): Morinaga A, Hasegawa K, Nomura R, Ookoshi T, Ozawa D, Goto Y, Yamada M, Naiki H
  • Journal Title: Biochem Biophys Acta-Proteins and Proteomics Volume: 1804 Pages: 986-995
  • Peer Reviewed
• [Journal Article] Critical role of interfaces and agitation on the nucleation of Aβ amyloid fibrils at low concentrations of Aβ monomers. (2010)
  • Author(s): Morinaga A, Hasegawa K, Nomura R, Ookoshi T, Ozawa D, Goto Y, Yamada M, Naiki H.
  • Journal Title: Biochem Biophys Acta - Proteins and Proteomics 1804 Pages: 986-995
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid of Alzheimer patients promotes amyloid β-protein oligomerization. (2010)
  • Author(s): Ikeda T, Ono K, Elashoff D, Condron MM, Noguchi-Shinohara M, Yoshita M, Teplow DB, Yamada M.
  • Journal Title: J Alzheimers Dis 21 Pages: 81-86
  • Peer Reviewed
• [Journal Article] Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. (2010)
  • Author(s): Hirohata M, Yoshita M, Ishida C, Ikeda S-I, Tamaoka A, Kuzuhara S, Shoji M, Ando Y, Tokuda T, Yamada M.
  • Journal Title: Eur J Neurol 17 Pages: 823-829
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid of Alzheimer patients promotes amyloid R-protein oligomerization. (2010)
  • Author(s): Ikeda T, Ono K, Elashoff D, Condron MM, Noguchi-Shinohara M, Yoshita M, Teplow DB, Yamada M
  • Journal Title: J Alzheimers Dis Volume: 21 Pages: 81-86
  • Peer Reviewed
• [Journal Article] Effects of Sex Hormones on Alzheimer Disease-associated (3-Amyloid Oligomer Formation in vitro. (2010)
  • Author(s): Morinaga A, Ono K, Takasaki J, Ikeda T, Hirohata M, Yamada M
  • Journal Title: Exp Neurol Volume: 228 Pages: 298-302
  • Peer Reviewed
• [Journal Article] Curcumin and Alzheimer's disease. (2010)
  • Author(s): Hamaguchi T, Ono K, Yamada M
  • Journal Title: CNS Neurosci Ther Volume: 16 Pages: 285-297
  • Peer Reviewed
• [Journal Article] 脳アミロイドアンギオパチー (2010)
  • Author(s): 吉田光宏、山田正仁
  • Journal Title: 分子脳血管病 Volume: 4 Pages: 190-197
• [Journal Article] 脳アミロイドアンギオパチー (2010)
  • Author(s): 石田千穂、山田正仁
  • Journal Title: Clin Neurosci Volume: 28 Pages: 1683-685
• [Journal Article] Aβ免疫療法の臨床試験 (2010)
  • Author(s): 山田正仁
  • Journal Title: Dementia Jpn Volume: 241 Pages: 122-128
• [Journal Article] Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy (2010)
  • Author(s): Hirohata M, Yoshita M, Ishida C, Ikeda S-I, Tamaoka A, Kuzuhara S, Shoji M, Ando Y, Tokuda T, Yamada M
  • Journal Title: Eur J Neurol (in press)
  • Peer Reviewed
• [Journal Article] Critical role of interfaces and agitation on the nucleation of Aβ amyloid fibrils at low concentrations of Aβ monomers (2010)
  • Author(s): Morinaga A, Hasegawa K, Nomura R, Ookoshi T, Ozawa D, Goto Y, Yamada M, Naiki H
  • Journal Title: Biochem Biophys Acta-Proteins and Proteomics 1804 Pages: 986-995
  • Peer Reviewed
• [Journal Article] New therapeutic strategy for amyloidosis (2009)
  • Author(s): Morinaga A, Ono K, Yamada M
  • Journal Title: Future Neurol Volume: 4 Pages: 287-289
  • Peer Reviewed
• [Journal Article] Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloidβaggregation pathway (2009)
  • Author(s): Hamaguchi T, Ono K, Murase A, Yamada M
  • Journal Title: Am J Pathol Volume: 175 Pages: 2557-2565
  • Peer Reviewed
• [Journal Article] Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloid β aggregation pathway. (2009)
  • Author(s): Hamaguchi T, Ono K, Murase A, Yamada M.
  • Journal Title: Am J Pathol 175 Pages: 2557-2565
  • Peer Reviewed
• [Journal Article] Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloid β aggregation pathway (2009)
  • Author(s): Hamaguchi T, Ono K, Murase A, Yamada M
  • Journal Title: Am J Pathol 175 Pages: 2557-2565
  • Peer Reviewed
• [Journal Article] CSF α-synuclein levels in dementia with Lewy bodies and Alzheimer's disease (2009)
  • Author(s): Noguchi-Shinohara M, ---, Yamada M
  • Journal Title: Brain Res 1251 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Editorial : Anti-amyloidogenic/protein-misfolding therapies in amyloidosis and other protein-misfolding disorders (2008)
  • Author(s): Yamada M
  • Journal Title: Curr Pharm Design Volume: 14 Pages: 3203-3204
• [Journal Article] Non-steroidal anti-inflammatory drugs as anti-amyloidogenic compounds (2008)
  • Author(s): Hirohata M, Ono K, Yamada M
  • Journal Title: Curr Pharm Design 14 Pages: 3280-3294
  • Peer Reviewed
• [Journal Article] α-synuclein assembly as a therapeutic target of Parkinson's disease and related disorders (2008)
  • Author(s): Ono K, Hirohata M, Yamada M
  • Journal Title: Curr Pharm Design 14 Pages: 3247-3266
  • Peer Reviewed
• [Journal Article] Predicting cerebral amyloid angiopathy-realated intracerebral hemorrhages and other cerebrovascular disorders in Alzheimer's disease
  • Author(s): Yamada M
  • Journal Title: Front Neurol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cerebral amyloid anigopathy
  • Author(s): Yamada M, Naiki H
  • Journal Title: Prog Mol Biol Transl Sci Volume: (in press)
  • Peer Reviewed
• [Journal Article] Phenolic compounds prevent amyloidβ-protein oligomerization and synaptic dysfunction by site specific binding
  • Author(s): Ono K, Li L, Takamura Y, Yoshiike Y, Zhu L, Han F, Mao X, Ikeda T, Takasaki J-I, Nishijo H, Takashima A, Teplow DB, Zagorski MG, Yamada M
  • Journal Title: J Biol Chem Volume: (in press)
  • Peer Reviewed
• [Journal Article] Multiple cerebral infarcts with a few vasculitic lesions in the chronic stage of cerebral amyloid angiopathy related inflammation
  • Author(s): Sakai K, Hayashi S, Sanpei K, Yamada M, Takahashi H
  • Journal Title: Neuropathology Volume: (in press)
  • Peer Reviewed
• [Presentation] 脳アミロイドアンギオパチーと認知症・認知障害 (2011)
  • Author(s): 山田正仁
  • Organizer: 第30回日本認知症学会学術集会
  • Place of Presentation: タワーホール船堀(東京都)(招待講演)
  • Year and Date: 2011-11-11
• [Presentation] 脳アミロイドアンギオパチーの臨床病理 (2011)
  • Author(s): 山田正仁
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋国際会議場(名古屋市)(招待講演)
  • Year and Date: 2011-05-20
• [Presentation] The effects of phenolic compounds on Aβaggregation and cerebal Aβplaques and angiopathy (2010)
  • Author(s): Yamada M, Hamaguchi T, Ono K, Hirohata M, Morinaga A, Ikeda T, Takasaki J, Murase A
  • Organizer: 2^<nd> International CAA Conference
  • Place of Presentation: UCLA Medical Center(USA)
  • Year and Date: 2010-05-15
• [Presentation] The effects of phenolic compounds on Aβ aggregation and cerebal Aβ plaques and angiopathy. (2010)
  • Author(s): Yamada M, Hamaguchi T, Ono K, Hirohata M, Morinaga A, Ikeda T, Takasaki J, Murase A.
  • Organizer: The 2nd International CAA Conference.
  • Place of Presentation: Ronald Reagan UCLA Medical Center University of California(USA)
  • Year and Date: 2010-05-15
• [Presentation] The effects of phenolic compounds on Aβ aggregation and cerebal Aβ plaques and angiopathy (2010)
  • Author(s): Yamada M, Hamaguchi T, Ono K, Hirohata M, Morinaga A, Ikeda T, Takacaki J, Murace A
  • Organizer: 2^<nd> International CAA Conference
  • Place of Presentation: UCLA Medical Center (USA)
  • Year and Date: 2010-05-15
• [Presentation] Cerebral Amyloid Angiopathy : Epidemiology, Clinical Features and Genetic Risk Factors (2008)
  • Author(s): Yamada M
  • Organizer: The 11th International conference on Alzheimer's disease and Related Disorders
  • Place of Presentation: McCormick Place(USA)
  • Year and Date: 2008-07-29
• [Presentation] Cerebral amyloid angiopathy : Epidemiology, clinical features and genetic risk factors. (2008)
  • Author(s): Yamada M.
  • Organizer: The 11th International conference on Alzheimer's disease and Related Disorders.
  • Place of Presentation: Hyatt Regency McComick Place (USA)
• [Presentation] Cerebral Amyloid Angiopathy : Epidemiology, Clinical Features and Genetic Risk Factors (2008)
  • Author(s): Yamada M
  • Organizer: The 11th International conference on Alzheimer's disease and Related Disorders
  • Place of Presentation: Chicago
• [Book] アミロイドーシスー診療のすべて:ガイドライン完全解説 (2011)
  • Author(s): 山田正仁
  • Publisher: 医歯薬出版
• [Book] アミロイドーシス(今日の治療指針2011年版)(山口徹、北原光夫、福井次矢(編)) (2011)
  • Author(s): 山田正仁
  • Publisher: 医学書院、東京
• [Book] 山口徹、北原光夫、福井次矢(編)今日の治療指針(2011年版)アミロイドーシス (2011)
  • Author(s): 山田正仁
  • Publisher: 医学書院
• [Book] 脳アミロイドアンギオパチー (2009)
  • Author(s): 山田正仁、石田千穂
  • Publisher: 協和企画
• [Book] アミロイドアンギオパチー(脳卒中治療ガイドライン2009)(篠原幸人、小川彰、鈴木則宏、片山泰朗、木村彰男(編集)) (2009)
  • Author(s): 山田正仁、石田千穂
  • Publisher: 協和企画、東京
• [Book] 脳卒中ガイドライン2009 : VI-5. 脳アミロイドアンギオパチー (261-262ページ) (2009)
  • Author(s): 山田正仁, 石田千穂
  • Total Pages: 358
  • Publisher: 協和企画/脳卒中学会HP (http://www.jsts.gr.jp/jss08.html)
• [Book] 脳アミロイド・アンギオパチー (2008)
  • Author(s): 石田千穂, 山田正仁
  • Publisher: 診断と治療社