Development and clinical application of novel methods for diagnosis and therapy of Alzheimer disease by regulation of neurotoxic oligomer

• Project/Area Number: 19390233
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Hirosaki University
• Principal Investigator: SHOJI Mikio Hirosaki University, 大学院・医学研究科, 教授 (60171021)
• Co-Investigator(Kenkyū-buntansha): MATSBARA Etsuro 弘前大学, 大学院・医学研究科, 准教授 (70219468) ; KAWARABAYASHI Takeshi 弘前大学, 附属病院, 講師 (90186156) ; WATANABE Mitsunori 弘前大学, 附属病院, 助教 (90251107) ; 冨山 誠彦 弘前大学, 大学院・医学研究科, 准教授 (40311542) ; 鈴木 千恵子 弘前大学, 医学部附属病院, 助教 (50396404)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2009: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2008: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2007: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 神経病態生化学 / アルツハイマー病 / オリゴマー / 診断 / 治療 / 臨床応用

Research Abstract

Recent studies suggest that oligomers are direct pathogenic agents to cause synaptic and neuronal disturbance in dementia patients including Alzheimer's disease. In this study, we established special antibodies to Ass, tau and α-synuclein to develop ELISA and detection systems, showing soluble oligomers, naturally occurred anti-Ass antibodies in brains and CSF in AD patients. Model mice of DLB (TgSNY) and AD (2xTgTau+/-APP+/-) were established. The pathological cascades of Ass induced tauopathy using 2xTgTau+/-APP+/- and NFT formation and neuronal cell deaths using by micro arrays were elucidated. Many biological pathways involved in these final cascades. Administration of anti-Ass antibodies reduced Ass burden and Ass oligomer in mice brains and increased in Ass monomer in CSF and plasma. Thus, anti-oligomer therapy is a possible agent for cure of neurodegenerative dementia.

Research Products

• [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: European Journal of Neurology
  • Peer Reviewed
• [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
  • Journal Title: J Neurosci 30(14) Pages: 4857-67
  • Peer Reviewed
• [Journal Article] Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. 2010 Feb 11.[Epub ahead of print] (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: European Journal of Neurology
  • Peer Reviewed
• [Journal Article] Japanese Genetic Study Consortium for Alzheimer Disease. 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
  • Journal Title: Genomics 63 Pages: 441-8
  • Peer Reviewed
• [Journal Article] Ataxia with oculomotor apraxia type 2 : clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients (2009)
  • Author(s): Anheim M, Monga B, Fleury M, Charles P, Barbot C, Salih M, Delaunoy JP, Fritsch M, Arning L, Synofzik M, Schols L, Sequeiros J, Goizet C, Marelli C, Le Ber I, Koht J, Gazulla J, De Bleecker J, Mukhtar M, Drouot N, Ali-Pacha L, Benhassine T, Chbicheb M, M'Zahem A, Hamri A, Chabrol B, Pouget J, Murphy R, Watanabe M, Coutinho P, Tazir M, Durr A, Brice A, Tranchant C, Koenig M
  • Journal Title: Brain 132(Pt 10) Pages: 2688-98
  • Peer Reviewed
• [Journal Article] A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human alpha-synuclein A30P+A53T transgenic mice (2009)
  • Author(s): Ono K, Ikemoto M, Kawarabayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, Shoji M, Takahashi M, Nakashima M
  • Journal Title: Parkinsonism Relat Disord 15(9) Pages: 649-54
  • Peer Reviewed
• [Journal Article] Motor impairment and aberrant production of neurochemicals in human alpha-synuclein A30P+A53T transgenic mice with alpha-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
  • Journal Title: Brain Res. 1250 Pages: 232-41
  • Peer Reviewed
• [Journal Article] GAB2 is not associated with late-onset Alzheimer's disease in Japanese (2009)
  • Author(s): Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R
  • Journal Title: Eur J Hum Genet 17(5) Pages: 682-6
  • Peer Reviewed
• [Journal Article] Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer's disease (2009)
  • Author(s): Wati H, Kawarabayashi T, Matsubara E, Kasai A, Hirasawa T, Kubota T, Harigaya Y, Shoji M, Maeda S
  • Journal Title: Brain Pathol 19(1) Pages: 48-57
  • Peer Reviewed
• [Journal Article] Ataxia with oculomotor apraxia type 2 : clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. (2009)
  • Author(s): Anheim M, Monga B, Fleury M, Charles P, Barbot C, Salih M, Delaunoy JP, Fritsch M, Arning L, Synofzik M, Schols L, Sequeiros J, Goizet C, Marelli C, Le Ber I, Koht J, Gazulla J, De Bleecker J, Mukhtar M, Drouot N, Ali-Pacha L, Benhassine T, Chbicheb M, M'Zahem A, Hamri A, Chabrol B, Pouget J, Murphy R, Watanabe M, Coutinho P, Tazir M, Durr A, Brice A, Tranchant C, Koenig M.
  • Journal Title: Brain 123 Pages: 2688-98
  • Peer Reviewed
• [Journal Article] An unusual case of chronic relapsing tetanus associated with mandibular 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.
  • Journal Title: Intern Med. 48 Pages: 1311-3
  • NAID: 130000121961
  • Peer Reviewed
• [Journal Article] Japanese Genetic Study Consortium for Alzheimer Disease. 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
  • Journal Title: Genomics 93 Pages: 441-8
  • Peer Reviewed
• [Journal Article] A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human alpha-synuclein A30P+A53T transgenic mice. (2009)
  • Author(s): Ono K, Ikemoto M, Kawarabayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, Shoji M, Takahashi M, Nakashima M.
  • Journal Title: Parkinsonism Relat Disord. 15 Pages: 649-54
  • Peer Reviewed
• [Journal Article] GAB2 is not associated with late-onset Alzheimer's disease in Japanese. (2009)
  • Author(s): Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R.
  • Journal Title: Eur J Hum Genet. 17 Pages: 682-6
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 東海林幹夫
  • Journal Title: アルツハイマー病.神経疾患最新の治療 2009-2011(小林祥泰,水澤英洋編)(南江堂) Pages: 179-183
• [Journal Article] (2009)
  • Author(s): 瓦林毅, 東海林幹夫
  • Journal Title: MCIと認知症-リスクファクター-Annual Review 2009神経(柳澤信夫,篠原幸人,岩田誠,清水輝夫,寺本明編)(中外医学社) Pages: 184-196
• [Journal Article] A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human alpha-synuclein A30P+A53T transgenic mice (2009)
  • Author(s): Ono K, Ikemoto M, Kawarabayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, Shoji M, Takahashi M, Nakashima M
  • Journal Title: Parkinsonism Relat Disord. Apr 1. [Epub ahead of print] PubMed PMID : 19345133
  • Peer Reviewed
• [Journal Article] Motor impairment and aberrant production of neurochemicals in human alpha-synuclein A30P+A53T transgenic mice with alpha-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
  • Journal Title: Brain Res 1250 Pages: 232-41
  • Peer Reviewed
• [Journal Article] Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction (2008)
  • Author(s): Kurata T, Hayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Kawarabayashi T, Takao Y, Ohta T, Harigaya Y, Manabe Y, Kamiya T, Shoji M, Abe K
  • Journal Title: Neurol Res. 30(8) Pages: 860-7
  • Peer Reviewed
• [Journal Article] Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury (2008)
  • Author(s): Jin G, Inoue M, Hayashi T, Deguchi K, Nagotani S, Zhang H, Wang X, Shoji M, Hasegawa M, Abe K
  • Journal Title: Neurol Res. 30(7) Pages: 731-9
  • Peer Reviewed
• [Journal Article] Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls (2008)
  • Author(s): Xu W, Kawarabayashi T, Matsubara E, Deguchi K, Murakami T, Harigaya Y, Ikeda M, Amari M, Kuwano R, Abe K, Shoji M
  • Journal Title: Brain Res. 1219 Pages: 169-79
  • Peer Reviewed
• [Journal Article] Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter (2008)
  • Author(s): Arai A, Tomiyama M, Kannari K, Kimura T, Suzuki C, Watanabe M, Kawarabayashi T, Shen H, Shoji M
  • Journal Title: Synapse 62(8) Pages: 632-5
  • Peer Reviewed
• [Journal Article] Microglial activation in brain lesions with tau deposits : comparison of human tauopathies and tau transgenic mice TgTauP301L (2008)
  • Author(s): Sasaki A, Kawarabayashi T, Murakami T, Matsubara E, Ikeda M, Hagiwara H, Westaway D, George-Hyslop PS, Shoji M, Nakazato Y
  • Journal Title: Brain Res. 1214 Pages: 159-68
  • Peer Reviewed
• [Journal Article] Plasma biomarkers of Alzheimer's disease (2008)
  • Author(s): Kawarabayashi T, Shoji M
  • Journal Title: Curr Opin Psychiatry 21(3) Pages: 260-7
  • Peer Reviewed
• [Journal Article] A small trinucleotide expansion in the TBP gene gives rise to a sporadic case of SCA17 with abnormal putaminal findings on MRI (2008)
  • Author(s): Watanabe M, Monai N, Jackson M, Yamamoto-Watanabe Y, Ikeda Y, Suzuki C, Tomiyama M, Kawarabayashi T, Kimura T, Seino Y, Wakasaya Y, Miki Y, Matsubara E, Shoji M
  • Journal Title: Intern Med 47(24) Pages: 2179-82
  • NAID: 130000079782
  • Peer Reviewed
• [Journal Article] A novel mutation in the arylsulfatase A gene associated with adult-onset metachromatic leukodystrophy without clinical evidence of neuropathy (2008)
  • Author(s): Suzuki C, Watanabe M, Tomiyama M, Sugimoto K, Nanba E, Jackson M, Kimura T, Seino Y, Wakasaya Y, Kawarabayashi T, Miki Y, Yamamoto-Watanabe Y, Shoji M
  • Journal Title: Eur Neurol 60(6) Pages: 310-1
  • Peer Reviewed
• [Journal Article] Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury (2008)
  • Author(s): Jin G, Inoue M, Hayashi T, Deguchi K, Nagotani S, Zhang H, Wang X, Shoji M, Hasegawa M, Abe K
  • Journal Title: Neurol Res 30(7) Pages: 731-9
  • Peer Reviewed
• [Journal Article] Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls (2008)
  • Author(s): Xu W, Kawarabayashi T, Matsubara E, Deguchi K, Murakami T, Harigaya Y, Ikeda M, Amari M, Kuwano R, Abe K, Shoji M
  • Journal Title: Brain Res 1219 Pages: 169-79
  • Peer Reviewed
• [Journal Article] Microglial activation in brain lesions with tau deposits : comparison of human tauopathies and tau transgenic mice TgTauP301L (2008)
  • Author(s): Sasaki A, Kawarabayashi T, Murakami T, Matsubara E, Ikeda M, Hagiwara H, Westaway D, George-HyslOp PS, Shoji M, Nakazato Y
  • Journal Title: Brain Res 1214 Pages: 159-68
  • Peer Reviewed
• [Journal Article] Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction Kamiya T, Shoji M, Abe K (2008)
  • Author(s): Kurata T, Hayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Kawarabayashi T, Takao Y, Ohta T, Harigaya Y, Manabe Y
  • Journal Title: Neurol Res 30(8) Pages: 860-7
  • Peer Reviewed
• [Journal Article] Clinical approach and pathological cascade of dementia (2008)
  • Author(s): Shoii M
  • Journal Title: Rinsho Shinkeigaku 48(7) Pages: 467-75
  • Peer Reviewed
• [Journal Article] Exacerbation of chronic pancreatitis induced by anticholinesterase medications in myasthenia gravis (2008)
  • Author(s): Tomiyama M, Shoji M
  • Journal Title: Eur J Neurol 15(5) Pages: 40-41
  • Peer Reviewed
• [Journal Article] The Japanese Genetic Study Consortium for Alzheimer's Disease, Consortium Information : Members are listed in the acknowledgements. Genetic association of CTNNA3 with late-onset Alzheimer's disease in females (2007)
  • Author(s): Miyashita A, Arai H, Asada T, Imagawa M, Matsubara E, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R
  • Journal Title: Hum Mol Genet 16(23) Pages: 2854-2869
  • Peer Reviewed
• [Journal Article] Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor protein and presenilin-1 (2007)
  • Author(s): Kurata T, Kawarabayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Ikeda M, Matsubara E, Westaway D, Hyslop PS, Harigaya Y, Kamiya T, Shoji M, Abe K
  • Journal Title: J Neurosci Res. 85(10) Pages: 2246-52
  • Peer Reviewed
• [Journal Article] PINK1, a gene product of PARK6, accumulates in α-synucleinopathy brains (2007)
  • Author(s): Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe K
  • Journal Title: J Neurol Neurosurg Psychiatry 78(6) Pages: 653-4
  • Peer Reviewed
• [Journal Article] Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis (2007)
  • Author(s): Nagata T, Ilieva H, Murakami T, Shiote M, Narai H, Ohta Y, Hayashi T, Shoji M, Abe K
  • Journal Title: Neurol Res. 29(8) Pages: 767-71
  • Peer Reviewed
• [Journal Article] Asian origin for the worldwide-spread mutational event in Machado-Joseph disease (2007)
  • Author(s): Martins S, Calafell F, Gaspar C, Wong VC, Silveira I, Nicholson GA, Brunt ER, Tranebjaerg L, Stevanin G, Hsieh M, Soong BW, Loureiro L, Durr A, Tsuji S, Watanabe M, Jardim LB, Giunti P, Riess O, Ranum LP, Brice A, Rouleau GA, Coutinho P, Amorim A, Sequeiros J
  • Journal Title: Arch Neurol 64(10) Pages: 1502-8
  • Peer Reviewed
• [Journal Article] Familial amyloid polyneuropathy (Finnish type) in a Japanese family : Clinical features and immunocytochemical studies (2007)
  • Author(s): Ikeda M, Mizushima K, Fujita Y, Watanabe M, Sasaki A, Makioka K, Enoki M, Nakamura M, Otani T, Takatama M, Okamoto K
  • Journal Title: J Neurol Sci. 252(1) Pages: 4-8
  • Peer Reviewed
• [Journal Article] Genetic association of CTNNA3 with late-onset Alzheimer's disease in females (2007)
  • Author(s): Miyashita A, Arai H, Asada T, Imagawa M, Matsubara E, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R
  • Journal Title: Hum Mol Genrt 16 Pages: 2854-2869
  • Peer Reviewed
• [Journal Article] Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor protein and presenilin-1 (2007)
  • Author(s): Kurata T, Kawarabayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Ikeda M, Matsubara E, Westaway D, Hyslop PS, Harigaya Y, Kamiya T, Shoji M, Abe K
  • Journal Title: J Neurosci Res 85 Pages: 22462252-22462252
  • Peer Reviewed
• [Journal Article] PINK1, a gene product of PARK6, accumulates in {alpha}-synucleinopathy brains (2007)
  • Author(s): Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe K
  • Journal Title: J Neurol Neurosurg Psychiatry 78 Pages: 653-654
  • Peer Reviewed
• [Journal Article] Different expression of low density lipoprotein receptor and ApoE between young adult and old rat brains after ischemia (2007)
  • Author(s): Hayashi T, Kamada H, Jin G, Deguchi K, Nagotani S, Sehara Y, Zhang H, Nagano I, Shoji M, Abe K
  • Journal Title: Neurol Res 28 Pages: 822-825
  • Peer Reviewed
• [Journal Article] Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis (2007)
  • Author(s): Nagata T, Ilieva H, Murakami T, Shiote M, Narai H, Ohta Y, Hayashi T, Shoji M, Abe K
  • Journal Title: Neurol Res 29 Pages: 767-771
  • Peer Reviewed
• [Journal Article] Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients (2007)
  • Author(s): Nagata T, Nagano I, Shiote M, Narai H, Murakami T, Hayashi T, Shoji M, Abe K
  • Journal Title: Neurol Res 29 Pages: 772-776
  • Peer Reviewed
• [Journal Article] A unique case of limb-girdle muscular dystrophy type 2A carrying novel compound heterozygous mutations in the human CAPN3 gene (2007)
  • Author(s): Matsubara E, Tsuchiya A, Minami N, Nishino I, Pappolla MA, Shoji M, Abe K
  • Journal Title: Eur J Neurol 14 Pages: 819-822
  • Peer Reviewed
• [Journal Article] Two cases of spinocerebellar ataxia accompanied by involvement of the skeletal motor neuron system and bulbar palsy (2007)
  • Author(s): Ohta Y, Hayashi T, Nagai M, Okamoto M, Nagotani S, Nagano I, Ohmori N, Takehisa Y, Murakami T, Shoji M, Kamiya T, Abe K
  • Journal Title: Intern Med 46 Pages: 751-755
  • NAID: 130000076727
  • Peer Reviewed
• [Journal Article] アキレス腱反射減弱をともなった30歳代の認知症例 (2007)
  • Author(s): 鈴木千恵子, 新井陽, 木村珠喜, 若佐谷保仁, 清野祐輔, 冨山誠彦, 馬場正之, 東海林幹夫, 杉本一博
  • Journal Title: 臨床脳波 49 Pages: 369-372
  • Peer Reviewed
• [Presentation] 認知症 : 診断と治療 (2009)
  • Author(s): 東海林幹夫
  • Organizer: 第19回日本臨床精神神経薬理学会, 第39回日本神経精神薬理学会
  • Place of Presentation: 京都, 国際会館
  • Year and Date: 2009-11-14
• [Presentation] 認知症の診断と治療 (2009)
  • Author(s): 東海林幹夫
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20
• [Presentation] Immune response to Aβ40 and Aβ42 in normal controls and patients with Alzheimer's disease (2009)
  • Author(s): Mikio Shoji
  • Organizer: The 11the meeting of Hirosaki International Forum of Medical Science
  • Place of Presentation: Hirosaki
• [Presentation] Recent advances of Alzheimer disease research : diagnosis and therapy (2009)
  • Author(s): Mikio Shoji
  • Organizer: The 2009 International Symposium on early detection and rehabilitation of dementia
  • Place of Presentation: Okayama
• [Presentation] Recent advances of Alzheimer disease research : diagnosis and therapy. (2009)
  • Author(s): Mikio Shoji
  • Organizer: The 2009 International Symposium on early detection and rehabilitation of dementia.
  • Place of Presentation: Okayama
• [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, Shoji M
  • Organizer: Neuroscience 2009, the Society for Neuroscience, 39^<th> Annual Meeting
  • Place of Presentation: Chicago
• [Presentation] The clinical characterization of the Japanese pedigree of FAD with PS1 H163R mutation. (2009)
  • Author(s): Miyagawa T, Iwata A, Kowa H, Kawarabayashi T, Shoji M, Tsuji S, Momose T, Kojima Y
  • Organizer: Alzheimer's Association 2009 International Conference on Alzheimer's disease(ICAD)
  • Place of Presentation: Vienna
• [Presentation] Niemann-Pick type C1遺伝子のloss of functionはlipid raftsでtau蓄積を促進する (2009)
  • Author(s): 瓦林毅, 若佐谷保仁, 渡辺有希子, 中畑直子, 高村歩美, 渡辺光法, 松原悦朗, 東海林幹夫
  • Organizer: 第28回日本認知症学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Tauopathyによる神経細胞死を誘導する因子の解析 (2009)
  • Author(s): 若佐谷保仁, 瓦林毅, 清野祐輔, 渡辺有希子, 渡辺光法, 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
• [Presentation] Clinical and molecular genetic study of ataxia-ocular apraxia 2 and functional analysis of senataxin (2008)
  • Author(s): Watanabe M, Jackson M, Fujimuro M, Kawarabayashi T, Seino Y, Wakasaya Y, Yamamoto-Watanabe Y, Matsubara E
  • Organizer: Society for neuroscience
  • Place of Presentation: washington
  • Year and Date: 2008-11-18
• [Presentation] Tauopahtyによる神経細胞死を誘導する因子の解析 (2008)
  • Author(s): 若佐谷保仁, 清野祐輔, 瓦林毅, 中畑直子, 渡辺光法, 東海林幹夫
  • Organizer: 日本認知症学会
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-10
• [Presentation] もの忘れ外来の軽度認知障害診断における日本語版ウエクスラー記憶検査法(WMS-R)の有用性 (2008)
  • Author(s): 中畑直子, 瓦林毅, 清野祐輔, 若佐谷保仁, 渡辺光法, 東海林幹夫
  • Organizer: 日本認知症学会
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-10
• [Presentation] CSF tau correlates with brain tau in tau transgenic mice (2008)
  • Author(s): Kawarabayshi T, Wakasaya Y, Seino Y, Watanabe M, Kimura T, Suzuki C, Tomiy ama M, Matsubara E, Ishiguro K, Westaway D, St. Geo rge-Hyslop P, Shoji M
  • Organizer: International Conference on Alzheimer's Di sease
  • Place of Presentation: Chicago
  • Year and Date: 2008-07-27
• [Presentation] 神経原線維変化と神経細胞死を再現するタウマウスモテルの作成 (2008)
  • Author(s): 瓦林毅, 清野祐輔, 若佐谷保仁, 渡辺光法, 木村珠喜, 鈴木千恵子, 冨山誠彦, 東海林幹夫, 松原悦朗, 池田将樹, 針谷康夫
  • Organizer: 日本老年医学会
  • Place of Presentation: 千葉
  • Year and Date: 2008-06-20
• [Presentation] 脳脊髄液タウは脳タウ蓄積と相関する (2008)
  • Author(s): 瓦林毅, 清野祐輔, 若佐谷保仁, 渡辺光法, 木村珠喜, 鈴木千恵子, 冨山誠彦, 東海林幹夫, 松原悦朗, 石黒幸一
  • Organizer: 日本神経学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-17
• [Presentation] Ataxia-ocularapr axia2(AOA2)の臨床遺伝学的検討とsenataxinの機能解析 (2008)
  • Author(s): 渡辺光法, 藤室雅弘, 冨山誠彦, 瓦林毅, 鈴木千恵子, 木村珠喜, 三木康生, 若佐谷保仁, 清野祐輔, 東海林幹夫
  • Organizer: 日本神経学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] Aβアミロイドはタウ蓄積を促進する (2008)
  • Author(s): 清野祐輔, 瓦林毅, 若佐谷保仁, 渡辺光法, 木村珠喜, 鈴木千恵子, 冨山誠彦, 東海林幹夫, 松原悦朗
  • Organizer: 日本神経学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] 当科におけるもの忘れ外来と脳脊髄液診断の現状 (2008)
  • Author(s): 若佐谷保仁, 瓦林毅, 中畑直子, 清野祐輔, 渡辺光法, 木村珠喜, 鈴木千恵子, 冨山誠彦, 東海林幹夫, 松原悦朗, 桑野良三
  • Organizer: 日本神経学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] CSF Tau correlates with Brain Tau In Tau Transgenic Mice (2008)
  • Author(s): Takeshi Kawarabayashi, Yusuke Seino, Yasuhito Wakasaya, Mitsunori Watanabe, Tamaki Kimura, Chieko Suzuki, Masahiko Tomiyama, Etsuro Matsubara, Koichi Ishiguro, David Westaway, Peter St. George-Hyslop, Mikio Shoji
  • Organizer: ICAD2008
  • Place of Presentation: Chicago
• [Presentation] Components of Lewy bodies. (2007)
  • Author(s): Mikio Shoji
  • Organizer: IPA 2007 Osaka SilverCongress
  • Place of Presentation: Osaka
  • Year and Date: 2007-10-18
• [Presentation] 認知症:早期診断と治療 (2007)
  • Author(s): 東海林幹夫
  • Organizer: 第183回日本内科学会東北地方会, 第50回生涯教育講演会
  • Place of Presentation: 弘前
  • Year and Date: 2007-09-01
• [Presentation] Ass oligomer : An essential therapeutic target for Alzheimer's disease. Brain'07 and Brain PET'07 (2007)
  • Author(s): Mikio Shoji
  • Organizer: The 23rd International Synmpsium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka
  • Year and Date: 2007-05-22
• [Presentation] An essential therapeutic target for Alzheimer's disease. (2007)
  • Author(s): Mikio Shoji
  • Organizer: Brain'07 and BrainPET'07, The 23rd lnternational Synmpsium on Cerebralk Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka
  • Year and Date: 2007-05-22
• [Presentation] Tauopathyによる神経細胞死を誘導する因子の解析 (2007)
  • Author(s): 東海林幹夫
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-17
• [Presentation] Niemann-Pick type C1遺伝子のloss of functionはtauopathyを促進する (2007)
  • Author(s): 東海林幹夫, 瓦林毅, 清野祐輔, 若佐谷保仁, 新井陽, 木村珠喜, 鈴木千恵子, 冨山誠彦, 村上哲郎, 倉田智子, 松原悦朗, 東海林幹夫
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-17
• [Presentation] 超高齢者集団認知症検診におけるMini-Mental State Examination(MMSE)の妥当性の検討 (2007)
  • Author(s): 若佐谷保仁、清野祐輔、瓦林毅、三木康生、木村珠喜、鈴木千恵子、渡辺光法、冨山誠彦、桑野良三、東海林幹夫
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-17
• [Presentation] Aβアミロイド蓄積は神経突起およびグリア細胞へのtau蓄積を促進する (2007)
  • Author(s): 清野祐輔, 瓦林毅, 若佐谷保仁, 新井陽, 木村珠喜, 鈴木千恵子, 冨山誠彦, 村上哲郎, 倉田智子, 松原悦朗, 東海林幹夫
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-17
• [Presentation] Aβ oligomerは脳アミロイド蓄積を促進する (2007)
  • Author(s): 針谷康夫, 松原悦朗, 池田将樹、瓦林毅, 東海林幹夫
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-16
• [Presentation] 生化学・血液マーカーはどこまで進歩したのか;現状と課題を再考する. (2007)
  • Author(s): 東海林幹夫
  • Organizer: アルツハイマー型痴呆研究会, 第八回学術シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-04-14
• [Presentation] Enhanced GABA release in the medial globus pallidus of a rat model of L-DOPA-induced dyskinesia (2007)
  • Author(s): Tomiyama M, Arai A, Kimura T, Watanabe M, Kawarabayashi T, Shoji M
  • Organizer: XVII WFN World Congress on Parkinson's Disease and Related Disorders
  • Place of Presentation: Amsterdam
• [Presentation] Analysis of amyloid angiopathy in Tg2576 Transgenic mouse model of Alzheimer's disease (2007)
  • Author(s): T. Kawarabayashi, Y. Seino, Y. Wakasaya, T. Kimura, C. Suzuki, M. Tomiyama, E. Matsubara, M. Shoji
  • Organizer: Brain'07 and Brain PET'07
  • Place of Presentation: Osaka
• [Presentation] Cortical neuronal and glial pathology in TgTauP301L transgenic mice (2007)
  • Author(s): T. Kawarabayashi, Y. Seino, Y. Wakasaya, M. Watanabe, C. Suzuki, M. Tomiyama, E. Matsubara, N. Egashira, M. Takahashi, M. Fujiwara, G. A. Carlson, D. Westaway, P. S. George-Hyslop, M. Shoji
  • Organizer: XVII WFN World Congress on Parkinson's Disease and Related Disorders
  • Place of Presentation: Amsterdam
• [Presentation] Multiple Sclerosis with chronic sialadenitis (2007)
  • Author(s): C. Suzuki, M. Tomiyama, T Kawara bayashi, M. Shoji, M Baba
  • Organizer: 17th meeting of the European Neurological Society
  • Place of Presentation: Rhodes Greece
• [Presentation] XVII WFN World Congress on Parkinson's Disease and Related Disorders (2007)
  • Author(s): T Kimura, M Tomiyama, A Arai, C Suzuki, T Kawarabayashi, M Shoji. Onset age or treatment age: Whichis a more important risk factor for L-DOPA-induced dyskinesia in Park inson's disease?
  • Organizer: XVII WFN World Congress on Parkinson's Disease and Related Disorders
  • Place of Presentation: Amsterdam
• [Presentation] Analysis of phosphorylation of tau in transgenic mice overexpressing GSK-3β (2007)
  • Author(s): Masaki Ikeda, Ilse Goris, Atsushi Sasaki, Takeshi Kawarabayashi, Yasuo Harigaya, Mikio Shoji, Dieder Moechars, Koichi Okamoto
  • Organizer: Neuroscience 2007, the Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] Characterization of therapeutic antibody against Aβ oligomers for Alzheimer's disease (2007)
  • Author(s): H. Sun, Y. Okamoto, T. Kawarabayashi, T. Yokoseki, M. Shibata, M. Morishima, Y. Saito, S. Murayama, Y. Ihara, M. Shoji, M. Michikawa, E. Matsubara
  • Organizer: Neuroscience 2007, the Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] Enhanced accumulation of phosphorylated a-synuclein in double transgenic mice expressing mutant bAPP and presenilin-1 (2007)
  • Author(s): Kurata T, Kawarabayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Ikeda M, Matsubara E, Westaway D, yslop PS, Harigaya Y, Kamiya T, Shoji M, Abe K
  • Organizer: IPA 2007 Osaka Siver Congress
  • Place of Presentation: Osaka
• [Presentation] Analysis of transgenic mice overexpressing mutant tau and GSK-3β (2007)
  • Author(s): Ikeda M, Goris I, Sasaki A, Kawarabayashi T, Ishiguro K, Shoji M, Harigaya Y, Dieder M, Okamoto K.
  • Organizer: IPA 2007 Osaka Siver Congress
  • Place of Presentation: Osaka
• [Presentation] Aβ accumulation causes postsynaptic damage in Tg2576 mice (2007)
  • Author(s): Y. Wakasaya, Y. Seino, T. Kawarabayashi, M. Watanabe, C. Suzuki, M. Tomiyama, E. Matsubara, M. Shoji,
  • Organizer: 日本認知症学会
  • Place of Presentation: 大阪
• [Presentation] Aβ amyloid accelerates accumulation of tau in neuronal processes (2007)
  • Author(s): Y. Seino, Y. Wakasaya, T. Kawarabayashi, M. Watanabe, C. Suzuki, M. Tomiyama, E. Matsubara, M. Shoji
  • Organizer: 日本認知症学会
  • Place of Presentation: 大阪
• [Presentation] Enhanced accumulation of phosphorylated α-synuclein in transgenic mice expressing APP and PS-1 (2007)
  • Author(s): Kurata T, Kawarabayashi T, Murakami T, Nagai M, Takehisa Y, Hayashi T, Kamiya T, Shoji M, Abe K
  • Organizer: 日本認知症学会
  • Place of Presentation: 大阪
• [Presentation] Tg2576トランスジェニックマウスにおけるミクログリア活性化状態について (2007)
  • Author(s): 佐々木惇、東海林幹夫、瓦林毅、針谷康夫、池田将樹、中里洋一
  • Organizer: 第49回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京
• [Book] アルツハイマー病. 神経疾患最新の治療 (2009)
  • Author(s): 東海林幹夫
  • Publisher: 南江堂
• [Book] 認知症の検査, 評価尺度, 認知症テキストブック (2008)
  • Author(s): 東海林幹夫
  • Publisher: 中外医学社
• [Book] アルツハイマー病の診断 (2008)
  • Author(s): 東海林幹夫
  • Publisher: 日本臨床社
• [Book] アルツハイマー病, 神経疾患最新の治療(小林祥泰, 水澤英洋編) (2008)
  • Author(s): 東海林幹夫
  • Publisher: 南江堂, 東京
• [Book] アルツハイマー病, 認知症テキストブック(認知症学会編) (2008)
  • Author(s): 東海林幹夫
  • Publisher: 中外医学社
• [Book] MCIと認知症-リスクファクター, AnnualReview神経2009 (2008)
  • Author(s): 瓦林毅, 東海林幹夫
  • Publisher: 南江堂
• [Book] アルツハイマー病(pp213-219, 241-246) (2007)
  • Author(s): 東海林幹夫
  • Total Pages: 580
  • Publisher: 日本臨床社,大阪
• [Book] 今日の治療指針, 2007年度版(pp651-562) (2007)
  • Author(s): 東海林幹夫
  • Total Pages: 1668
  • Publisher: 医学書院,東京
• [Book] 神経難病のすべて〜症状・診断から最先端治療, 福祉の実際まで(pp34-43) (2007)
  • Author(s): 瓦林毅, 東海林幹夫
  • Total Pages: 389
  • Publisher: 新興医学,東京
• [Book] 医学のあゆみ, 別冊(pp71-76) (2007)
  • Author(s): 瓦林毅, 東海林幹夫
  • Total Pages: 131
  • Publisher: 医歯薬出版株式会社,東京
• [Book] 軽度認知障害(pp47-59) (2007)
  • Author(s): 瓦林毅, 東海林幹夫
  • Total Pages: 293
  • Publisher: 中外医学社,東京
• [Remarks]
• [Remarks]
  • URL: http://www.med.hirosaki-u.ac.jp/~neurology/index.php
• [Remarks]
  • URL: http://www.med.hirosaki-u.ac.jp/~neurology/index.php
• [Patent(Industrial Property Rights)] アルツハイマー病の検査法, アルツハイマー病に対して治療効果を有する物質のスクリーニング方法およびアルツハイマー病の検査キット (2010)
  • Inventor(s): 東海林幹夫, 渡辺光法
  • Industrial Property Rights Holder: 弘前大学, 北海道大学
  • Industrial Property Number: 2010-048003
  • Filing Date: 2010-03-04
• [Patent(Industrial Property Rights)] アルツハイマー病の検査法,アルツハイマー病に対して治療効果を有する物質のスクリーニング方法およびアルツハイマー病の検査キット (2010)
  • Inventor(s): 東海林幹夫, 渡辺光法
  • Industrial Property Rights Holder: 弘前大学
  • Industrial Property Number: 2010-048003
  • Filing Date: 2010-03-04
• [Patent(Industrial Property Rights)] ワクチンを蓄積する形質転換ダイズ植物およびその利用 (2008)
  • Inventor(s): 東海林幹夫, 瓦林毅
  • Industrial Property Rights Holder: 弘前大学, 京都大学, 北興化学
  • Industrial Property Number: 2008-301006
  • Filing Date: 2008-11-28
• [Patent(Industrial Property Rights)] パーキンソン病モデルトランスジェニックマウス (2008)
  • Inventor(s): 東海林幹夫, 池田将樹, 山田秀一
  • Industrial Property Rights Holder: 東海林幹夫, 池田将樹, 山田秀一
  • Filing Date: 2008-08-22