Development of therapies targeting pathogenic oligomers in lipid rafts
Project/Area Number |
21591069
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Hirosaki University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
SHOJI Mikio 弘前大学, 大学院・医学研究科, 教授 (60171021)
渡辺 光法 弘前大学, 大学院・医学研究科, 助教 (90251107)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 神経分子病態学 / リピドラフト / タウ / シヌクレイン / アミロイドss蛋白 / オリゴマー / NMDA受容体 / トランスジェニックマウス / アルツハイマー病 / 信号伝達系 / アミロイドβ蛋白 / コレステロール |
Research Abstract |
Lipid rafts are crucial modulators of amyloid ss protein (Aβ) production and aggregation, leading to the accumulation of neurotoxic Aβ oligomers in the brain. Recent findings suggest that lipid rafts are pathological signaling platforms where Aβ oligomers exert synaptic failure and neurotoxicity. Thus lipid rafts are attracted as the target for therapy of Alzheimer's disease (AD). In other neurodegenerative diseases, lipid rafts are also thought to be sites for aggregation and neurotoxicity.
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Report
(4 results)
Research Products
(209 results)
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[Journal Article] Sortilin is required for toxic action of Aβ oligomers (AβOs) : Extracellular AβOs trigger apoptosis,and intraneuronal AβOs impair degradation pathways2012
Author(s)
Takamura A, Sato Y, Watabe D, Okamoto Y, Nakata T, Kawarabayashi T, Oddo S, Laferla FM, Shoji M, Matsubara E
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[Journal Article] the Japanese Alzheimer's Disease Neuroimaging Initiative. Altered γ-secretase activity in mild cognitive impairment and Alzheimer's disease2012
Author(s)
Kakuda N, Shoji M, Arai H, Furukawa K, Ikeuchi T, Akazawa K, Takami M, Hatsuta H, Murayama S, Hashimoto Y, Miyajima M, Arai H, Nagashima Y, Yamaguchi H, Kuwano R, Nagaike K, Ihara Y
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Journal Title
EMBO Mol Med
Volume: 4
Pages: 344-352
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[Journal Article] Altered Y-secretase activity in mild cognitive impairment and Alzheimer's disease2012
Author(s)
Kakuda N, Shoji M, Arai H, Furukawa K, Ikeuchi T, Akazawa K, Takami M, Hatsuta H, Murayama s, Hashimoto Y, Miyajima M, Arai H, Nagashima Y Yamaguchi H, Kuwano R, Nagaike K, Ihara Y ; the Japanese Alzheimer's Disease Neuroimaging Initiative
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Journal Title
Eur J Neurol
Volume: 4
Issue: 4
Pages: 344-352
DOI
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[Journal Article] Dissociation of Aβ from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates Aβ42 assembly2011
Author(s)
Takamura A, Kawarabayashi T, Yokoseki T, Shibata M, Morishima-Kawashima M, Saito Y, Murayama S, Ihara Y, Abe K, Shoji M, Michikawa M, Matsubara E
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Journal Title
J Neurosci Res
Volume: 89
Pages: 815-821
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[Journal Article] Extracellular and intraneuronal HMW-AβOs represent a molecular basis of memory loss in Alzheimer's disease model mouse2011
Author(s)
Takamura A, Okamoto Y, Kawarabayashi T, Yokoseki T, Shibata M, Mouri A, Nabeshima T, Sun H, Abe K, Urisu T, Yamamoto N, Shoji M, Yanagisawa K, Michikawa M, Matsubara E
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Journal Title
Mol Neurodegener
Volume: 6
Pages: 20-20
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[Journal Article] Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy2011
Author(s)
Wakasaya Y, Kawarabayashi T, Watanabe M, Yamamoto-Watanabe Y, Takamura A, Kurata T, Murakami T, Abe K, Yamada K, Wakabayashi K, Sasaki A, Westaway D, St.George-Hyslop P, Matsubara E, Shoji M
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Journal Title
J Neurosci Res
Volume: 89
Pages: 576-584
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[Journal Article] Dissociation of beta-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer' s disease accelerates beta-amyloid-422011
Author(s)
Takamura A, Kawarabayashi T, Yokoseki T, Shibata M, Morishima-Kawashima M, Saito Y, Murayama S, Ihara Y, Abe K, Shoji M, Michikawa M, Matsubara E
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Journal Title
assembly. Neurosci Res
Volume: 89
Issue: 6
Pages: 815-821
DOI
Related Report
Peer Reviewed
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[Journal Article] Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse2011
Author(s)
Takamura A, Okamoto Y, Kawarabayashi T, Yokoseki T, Shibata M, Mouri A, Nabeshima T, Sun H, Abe K, Urisu T, Yamamoto N, Shoji M, Yanagisawa K, Michikawa M, Matsubara E
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Journal Title
Mol Neurodegener
Volume: 6
Issue: 1
Pages: 20-20
DOI
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[Journal Article] Dissociation of Aβ from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates Aβ42 assembly.2011
Author(s)
Takamura A, Kawarabavashi T, Yokoseki T, Shibata M, Morishima-Kawashima M, Sai to Y, Murayama S, Ihara Y, Abe K, Shoji M, Michikawa M, Matsubara E
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Journal Title
J Neurosci Res
Volume: Epub ahead of print
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Peer Reviewed
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[Journal Article] Extracellular and intraneuronal HMW-AbetaOs represent a molecul ar basis of memory loss in Aliheimer's disease model mouse.2011
Author(s)
Takamura A, Okamoto Y, Kawarabavashi T, Yokoseki T, Shibata M, Mouri A, Nabeshima T, Sun H, Abe K, Urisu T, Yamamoto N, Shoji M, Yanagisawa K, Michikawa M, Matsubara E
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Journal Title
Mol Neurodegener.
Volume: 60
Pages: 20-20
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[Journal Article] Aβ amyloid accelerates accumulation of phosphorylated tau in neuronal cytoplasm and processes of double transgenic mice2010
Author(s)
Seino Y, Kawarabayashi T, Wakasaya Y, Takamura A, Nakahata N, Watanabe M, Yamamoto-Watanabe Y, Matsubara E, Westaway D, Davis P, St.George-Hyslop P, Shoji M
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Journal Title
J Neurosci Res
Volume: 88
Pages: 3547-3554
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[Journal Article] A Japanese ALS6 family with mutation R521C in the FUS/TLS gene a clinical, pathological and genetic report2010
Author(s)
Yamamoto-Watanabe Y, Watanabe M, Okamoto K, Fujita Y, Jackson M, Ikeda M, Nakazato Y, Ikeda Y, Matsubara E, Kawarabayashi T, Shoji M
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Journal Title
J Neurol Sci
Volume: 296
Pages: 59-63
Related Report
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[Journal Article] Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST32010
Author(s)
Yamamoto-Watanabe Y, Watanabe M, Jackson M, Akimoto H, Sugimoto K, Yasujima M, Wakasaya Y, Matsubara E, Kawarabayashi T, Harigaya Y, Lyndon AR, Shoji M
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Journal Title
Brain Res
Volume: 1361
Pages: 140-145
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[Journal Article] Prevalence of autosomal dominant cerebellar ataxia in Aomori, the northernmost prefecture of Honshu, Japan2010
Author(s)
Yamamoto-Watanabe Y, Watanabe M, Hikichi M, Ikeda Y, Jackson M, Wakasaya Y, Matsubara E, Kawarabayashi T, Kannari K, Shoji M
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Journal Title
Internal Med
Volume: 49
Pages: 2409-2414
NAID
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[Journal Article] Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy.2010
Author(s)
Wakasaya Y, Kawarabayashi T, Watanabe M, Yamamoto-Watanabe Y, Takamura A, Kura ta T, Murakami T, Abe K, Y amada K, Wakabayashi K, Sasaki A, Westaway D, St.Geor ge-Hyslop P, Matsubara E, Shoji M
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Journal Title
J Neurosci Res
Volume: Epub ahea d of print
Related Report
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[Journal Article] Aβ amyloid accelerates accumulation of phosphorylated tau in neuronal cytoplasm and processes of double transgenic mice.2010
Author(s)
Seino Y, Kawarabayashi T, Wakasaya Y, Takamura A, Nakahata N, Watanabe M, Yamamoto-Watanabe Y, Matsubara E, Westaway D, Davis P, St.George-Hyslon P, Shaji
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Journal Title
J Neurosci Res
Volume: 88
Pages: 3547-3554
Related Report
Peer Reviewed
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[Journal Article] Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST3.2010
Author(s)
Yamamoto-Watanabe Y, Watanabe M, Jackson M, Akimoto H, Sugimoto K, Yasujima M, Wakasaya Y, Matsubara E, Kawarabayashi T, Harigaya Y, Lyndon AR, Shoji M
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Journal Title
Brain Res
Volume: 1361
Pages: 140-145
Related Report
Peer Reviewed
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[Journal Article] Prevalence of autosomal dominant cerebellar ataxia in Aomori, the northernmost prefbcture of Honshu, Japan.2010
Author(s)
Yamamoto-Watanabe Y, Watanabe M, Hikichi M, Ikeda Y, Jackson M, Wakasaya Y, Matsubara E, Kawarabayashi T, Kannari K, Shoji M
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Journal Title
Internal Med
Volume: 49
Pages: 2409-2414
Related Report
Peer Reviewed
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[Journal Article] A Japanese ALS6 family with mutation R521C in the FUS/TLS gene : a clinical, pathological and genetic report.2010
Author(s)
Yamamoto-Watanabe Y, Watanabe M, Okamoto K, Fujita Y, Jackson M, Ikeda M, Nakazato Y, Ikeda Y, Matsubara E, Kawarabayashi T, Shoji M
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Journal Title
J Neurol Sci.
Volume: 296
Pages: 59-63
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[Journal Article] Loss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans..2010
Author(s)
Perkins EM, Clarkson YL, Sabatier N, Longhurst DM, Mill ward CP, Jack J, Toraiwa J, Watanabe M, Rothstein JD, Lyndon AR, Wyllie DJ, Dutia MR Inekson M.
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Journal Title
J Neurosci
Volume: 30
Pages: 4857-4867
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[Journal Article] PAとPSPの重要な鑑別点.2010
Author(s)
倉田智子, 林健, 宮崎一徳, 森本展年, 大田泰之, 竹久康, 永井真貴子, 瓦林毅, 神谷達司, 東海林幹夫, 阿部康二, 高尾芳樹, 大田泰正, 針谷康夫, 真邊康宏
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Journal Title
老年期認知症研究会誌
Volume: 16
Pages: 125-131
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[Journal Article] Loss of{beta}-III spectrin leads to purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans.2010
Author(s)
Perkins EM, Clarkson YL, Sabatier N, Longhurst DM, Millward CP, Jack J, Toraiwa J, Watanabe M, Rothstein JD, Lyndon AR, Wyllie DJ, Dutia MB, Jackson M
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Journal Title
J Neurosci 30
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[Journal Article]2010
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瓦林毅, 東海林幹夫
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新しい診断と治療のABC 66認知症(最新医学社)
Pages: 148-160
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[Journal Article] Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology2009
Author(s)
Ikeda M, Kawarabayashi T, Harigaya Y, Sasaki A, Yamada S, Matsubara E, Murakami T, Tanaka Y, Kurata T, Wuhua X, Ueda K, Kuribara H, Ikarashi Y, Nakazato Y, Okamoto K, Abe K, Shoji M
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Journal Title
Brain Res
Volume: 1250
Pages: 232-241
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[Journal Article] A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human α-synuclein A30P+A53T transgenic mice2009
Author(s)
Ono K, Ikemoto M, Kawarabayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, Shoji M, Takahashi M, Nakashima M
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Journal Title
J Neurosci Res
Volume: 15
Pages: 649-654
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[Journal Article] An unusual case of chronic relapsing tetanus associated with mandibular osteomyelitis2009
Author(s)
Wakasaya Y, Watanabe M, Tomiyama M, Suzuki C, Jackson M, Fujimuro M, Kimura T, Seino Y, Kawarabayashi T, Yamamoto-Watanabe Y, Matsubara E, Shirahama I, Takamura A, Nakahata N, Shoji M
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Journal Title
Intern Med
Volume: 48
Pages: 1311-1313
NAID
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[Journal Article] Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology.2009
Author(s)
Ikeda M, Kawarabayashi T, Harigaya Y, Sasaki A, Yamada S, Matsubara E, Murakami T, Tanaka Y, Kurata T, Wuhua X, Ueda K, Kuribara H, Ikarashi Y, Nakazato Y, Okamoto K, Abe K, Shoji M
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Journal Title
Brain Res 1250
Pages: 232-241
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[Journal Article] A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human α-synuclein A30P+A53T transgenic mice.2009
Author(s)
Ono K, Ikemoto M, Kawara bayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, Shoji M, Takahashi M, Nakashima M
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Journal Title
Parkinsonism Relat Disord 15
Pages: 649-654
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[Journal Article] An unusual case of chronic relapsing tetanus associated with man dibular osteomyelitis.2009
Author(s)
Wakasaya Y, Watanabe M, Tomiyama M, Suzuki C, Jackson M, Fujimuro M, Kimura T, Seino Y, Kawarabayashi T, Yamamoto-Watanabe Y, Matsubara E, Shirahama I, Takamura A, Nakahata N, Shoji M
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Journal Title
Intern Med 48
Pages: 1311-1313
NAID
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[Journal Article] Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese.2009
Author(s)
Takei N, Miyashita A, Tsukie T, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kimura H, Kakita A, Takahashi H, Tsuji S, Kanazawa I, Ihara Y, Odani S, Kuwano R ; Japanese Genetic Study Consortium for Alzheimer Disease
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Journal Title
Genomics 93
Pages: 441-448
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[Journal Article]2009
Author(s)
瓦林毅, 東海林幹夫
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Journal Title
Annual Review 2009神経(中外医学社)
Pages: 184-196
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[Presentation] Neuroscience 20102010
Author(s)
Kawarabayashi T, Wakasaya Y, Watanabe M, Yamamoto-Watanabe Y, Takamura A, Matsubara E, Shoji M, Factors responsible for neurofibrillary tangle formation and neuronal cell loss in tauopathy brains
Organizer
the Society for Neuroscience, 40^<th> Annual Meeting
Place of Presentation
San Diego
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[Presentation] ALS6の臨床遺伝および病理学的検討2010
Author(s)
渡辺光法,渡辺有希子,岡本幸市,藤田行雄,池田将樹,中里洋一,白濱育美,高村歩美,瓦林毅,松原悦朗,池田佳生,若佐谷保仁,東海林幹夫
Organizer
第51回日本神経学会総会
Place of Presentation
東京
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[Presentation] 第51回日本神経学会総会2010
Author(s)
瓦林毅, 若佐谷保仁, 渡辺有希子, 渡辺光法, 松原悦朗, 東海林幹夫
Organizer
lipid raftsは神経変性疾患の共通した蛋白凝集開始部位である.
Place of Presentation
東京国際フォーラム(東京)
Related Report
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[Presentation] 第51回日本神経学会総会2010
Author(s)
松原悦朗, 高村歩美, 若佐谷保仁, 渡辺有希子, 中畑直子, 渡辺光法, 瓦林毅, 東海林幹夫
Organizer
ABオリゴマー特異的受動免疫予防法の開発.
Place of Presentation
東京国際フォーラム(東京)
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[Presentation] 第51回日本神経学会総会2010
Author(s)
渡辺光法, 渡辺有希子, 岡本幸市, 藤田行雄, 池田将樹, 中里洋一, 白濱育美, 高村歩美, 瓦林毅, 松原悦朗, 池田佳生, 若佐谷保仁, 東海林幹夫
Organizer
ALS6の臨床遺伝および病理学的検討
Place of Presentation
東京国際フォーラム(東京)
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[Presentation] 複数の脳血管障害のリスクファクターを有し,高齢で発症したCADASILの1例.2010
Author(s)
渡辺光法, 足立芳樹, 渡辺有希子, 白濱育美, 高村歩美, 中畑直子, 若佐谷保仁, 瓦林毅, 松原悦朗, 東海林幹夫
Organizer
第35回脳卒中学会総会
Place of Presentation
岩手県民会館(盛岡)
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[Presentation] diagnosis and therapy2009
Author(s)
Shoji M, Recent advances of Alzheimer disease research
Organizer
The 2009 International Symposium on Early Detection and Rehabilitation Early Detection and Rehabilitation
Place of Presentation
Okayama
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[Presentation] Measurement of cystatin C in cerebrospinal fluid of neurological disorders and analyses of +73 G/A polymorphism2009
Author(s)
Watanabe T, Yamamoto-Watanabe Y, Akimoto H, Sugimoto K, Yasujima M, Kawarabayashi T, Takamura A, Nakahata N, Shirahama I, Wakasaya Y, Matsubara E, Shoji M
Organizer
第32回日本分子生物学会年会
Place of Presentation
横浜
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[Presentation] 神経変性疾患における脳脊髄液シスタチンC測定の意義2009
Author(s)
渡辺光法,渡辺有希子,秋元広之,杉本一博,保嶋実,瓦林毅,高村歩美,中畑直子,白濱育美,若佐谷保仁,清野祐輔,松原悦朗,東海林幹夫
Organizer
50回日本神経学会総会
Place of Presentation
仙台
Related Report
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[Presentation] PAとPSPの重要な画像上の鑑別点2009
Author(s)
倉田智子,林健,村上哲郎,宮崎一徳,森本展年,太田康之,池田雅美,武久康,永井真貴子,池田佳生,瓦林毅,高尾芳樹,大田泰正,針谷康夫,真邊泰宏,神谷達司,東海林幹夫,阿部康二
Organizer
第50回日本神経学会総会
Place of Presentation
仙台
Related Report
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[Presentation] Accumulation of protein in lipid rafts in mouse models of neurodegenerative diseases.2009
Author(s)
Kawarabayashi T, Wakasaya Y, Seino Y, Takamura A, Nakahata N, Watanabe Y, Watanabe M, Matsubara E, Shoj M
Organizer
Neuroscience 2009, the Society for Neuroscience, 39^<th> Annual Meeting
Place of Presentation
Chicago
Related Report
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[Presentation] Measurement of cystatin C in cerebrospinal fluid of neurological disorders and analyses of +73 G/A polymorphism.2009
Author(s)
Watanabe T, Yamamoto-Watanabe Y, Akimoto H, Sugimoto K, Yasujima M, Kawarabayashi T, Takamura A, Nakahata N, Shirahama I, Wakasaya Y, Matsubara E, Shoji M
Organizer
第32回日本分子生物学会年会
Place of Presentation
横浜
Related Report
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[Presentation] 神経変性疾患における脳脊髄液シスタチンCの測定.2009
Author(s)
渡辺光法, 渡辺有希子, 秋元広之, 杉本一博, 保嶋実, 瓦林毅, 高村歩美, 中畑直子, 白濱育美, 若佐谷保仁, 清野祐輔, 松原悦朗, 東海林幹夫
Organizer
第50回日本神経学会総会
Place of Presentation
仙台
Related Report
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[Presentation] PAとPSPの重要な画像上の鑑別点.2009
Author(s)
倉田智子, 林健, 村上哲郎, 宮崎一徳, 森本展年, 太田康之, 池田雅美, 武久康, 永井真貴子, 池田佳生, 瓦林毅, 高尾芳樹, 大田泰正, 針谷康夫, 真邊泰宏, 神谷達司, 東海林幹夫, 阿部康二
Organizer
第50回日本神経学会総会
Place of Presentation
仙台
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[Book] アルツハイマー病
Author(s)
東海林幹夫
Publisher
別冊NHKきょうの健康「認知症」(印刷中)
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