The predictive or monitoring marker for Alzheimer's disease

• Project/Area Number: 18590968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Institute for Longevity Sciences,NCGG
• Principal Investigator: MATSUBARA Etsuo National Institute for Longevity Sciences,NCGG, National Center for Geriatrics and Gerontology, 室長 (70219468)
• Co-Investigator(Kenkyū-buntansha): SHOJI Mikio Hirosaki University, Graduate School of Medicine, Professor (60171021) ; ITO Nobuo Mie University, Graduate School of Medicine, Instructor (10362344) ; KAWARABAYASHI Takeshi Hirosaki University, Graduate School of Medicine, Assistant Professor (90186156)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Alzheimer's disease / ELISA / Aβ oligomers / marker

Research Abstract

In the present research, we have developed a sandwich ELISA specific to Aβ oligomers. The combination of this methodology with size exclusion chromatography allowed us to identify the presence of Aβ oligomers in human cerebrospinal fluid(CSF). It is well known that the levels of Aβ monomers was decreased in the CSF obtained from Alzheimer's disease(AD) compared to age-matched normal subjects. Interestingly, the levels of Aβ oligomers were increased in AD patients with a comcomitant reduction of Aβ monomers. Therefore, it is relevant to note that the measurement of the ratio, Aβ oligomers to monomers, was a potential tool to monitor the Alzheimer's disease. We also found that the administration of melatonin caused the elevation of Aβ in plasma obtained from the model mice of Alzheimer's disease, whch allowed us to see if which mice have an accumulation of Aβ in the brain. Our results may indicate that both could be a potential "surrogate marker" for AD.

Research Products

• [Journal Article] Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls. (2008)
  • Author(s): Xu W, Matsubara E, et. al.
  • Journal Title: Brain Res (Epub ahead of print)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Transthyretin Accelerates Vascular Abeta Deposition in a Mouse Model ol Alzheimer's Disease. (2008)
  • Author(s): Wati H, Kawarabayashi T, Matsubara E, Kasai A, Hirasawa T, Kubota T, Harigaya Y, Shoji M, Maeda S.
  • Journal Title: Brain Pathol 2008 Apr 22 (Epub ahead of print)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Microglial activation in brain lesions with tau deposits : Comparison ot human tauopathies and tau transgenic mice TgTau(P301L). (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
  • Description: 「研究成果報告書概要(欧文)」より
• [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 (Epub ahead of print)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病-基礎研究から予防・治療への新しいパラダイム- II基礎編 アルツハイマー病に関する基礎知識, Aβ化学構造の分解過程, Aβの化学構造. (2008)
  • Author(s): 松原悦朗, 柳澤勝彦.
  • Journal Title: 日本臨床(日本臨床社, 大阪) 66巻増刊号1 Pages: 61-66
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病-基礎研究から予防・治療への新しいパラダイム- III臨床編 アルツハイマー病の診断, 生物学的マーカー検査 脳脊髄液 タウ. (2008)
  • Author(s): 松原悦朗.
  • Journal Title: 日本臨床(日本臨床社, 大阪) 66巻増刊号1 Pages: 247-251
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病-基礎研究から予防・治療への新しいパラダイム- III臨床編 アルツハイマー病の新しい治療法の開発 新規医薬品 Aβ凝集抑制薬. (2008)
  • Author(s): 松原悦朗, 柳澤勝彦.
  • Journal Title: 日本臨床(日本臨床社, 大阪) 66巻増刊号1 Pages: 493-497
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病-基礎研究から予防・治療への新しいパラダイム- III臨床編 アルツハイマー病の新しい治療法の開発 Aβクリアランス経路を標的とした治療法の開発. (2008)
  • Author(s): 松原悦朗.
  • Journal Title: 日本臨床(日本臨床社, 大阪) 66巻増刊号1 Pages: 542-546
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病の最近の進歩 : アルツハイマー病の抗体治療 (2008)
  • Author(s): 松原悦朗.
  • Journal Title: 臨床検査 52(3) Pages: 297-301
  • Description: 「研究成果報告書概要(欧文)」より
• [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, Matsubara E, et. al.
  • Journal Title: Hum Mol Genet 16 Pages: 2854-2869
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A ganglioside-induced toxic soluble Abeta assembly.Its enhanced formation from Abeta bearing the Arctic mutation. (2007)
  • Author(s): Yamamoto N, Matsubara E, et. al.
  • Journal Title: J Biol Chem 282 Pages: 2646-2655
  • Description: 「研究成果報告書概要(和文)」より
  • 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 Pages: 2854-2869
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A ganghliside-induced toxic soluble Abeta assembly. Its enhanced formation from Abeta bearing the Arctic mutation. (2007)
  • Author(s): Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Murayama W, Michikawa M, Yanagisawa K
  • Journal Title: J Biol Chem 282(4) Pages: 2646-2655
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enhanced accumulation of phosphorylated alpha-synuclein 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
  • Description: 「研究成果報告書概要(欧文)」より
• [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(6) Pages: 653-4
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aβオリゴマー (2007)
  • Author(s): 松原悦朗.
  • Journal Title: Dementia Japan 21 Pages: 253-260
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病モデル動物におけるメラトニン療法 (2007)
  • Author(s): 松原悦朗.
  • Journal Title: Modern Physician 27(8) Pages: 1105-1108
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] トランスジェニックマウスを用いたアルツハイマー病発症機序の解析 (2007)
  • Author(s): 瓦林毅, 針谷康夫, 池田将樹, 岡本幸市, 東海林幹夫, 松原悦朗.
  • Journal Title: 老年期痴呆研究会誌 14 Pages: 9-11
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] アルツハイマー病動物モデルによる治療法開発 (2007)
  • Author(s): 松原悦朗.
  • Journal Title: 老年期痴呆研究会誌 14 Pages: 159-160
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic association of CTNNA3 with late-onset Alzheimer's disease in females. (2007)
  • Author(s): Miyashita A, Matsubara E, et. al.
  • Journal Title: Hum Mol Genet 16 Pages: 2854-2869
  • Peer Reviewed
• [Journal Article] A unique case of limb-girdle muscular atrophy type 2A carrying novel compound heterozygous mutations in the human CAPN3 gene. (2007)
  • Author(s): Matsubara E, et. al.
  • Journal Title: Eur J Neurol 14 Pages: 819-822
  • 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, Matsubara E, et. al.
  • Journal Title: J Neurosci Res 85 Pages: 2246-2252
  • Peer Reviewed
• [Journal Article] PINK1, a gene product of PARK6, accumulates in α-synucleinopathy brains. (2007)
  • Author(s): Murakami T, Matsubara E, et al.
  • Journal Title: J Neurol Neurosurg Psychiatry (Epub ahead of print)
• [Journal Article] A ganglioside-induced toxic soluble Aβassembly. Its enhanced formation from Aβ bearing Arctic mutation. (2007)
  • Author(s): Yamamoto N, Matsubara E, et al.
  • Journal Title: J Biol Chem 282 Pages: 2646-2655
• [Journal Article] Cortical neuronal and glial pathology in TgTauP301L transgenic mice : neuronal degeneration, memory disturbance, and phenotypic variation. (2006)
  • Author(s): Murakami T, Paitel E, Kawarabayashi T, Ikeda M, Chishti MA, Janus C, Matsubara E, Sasaki A, Kawarai T, Phinney AL, Harigaya Y, Home P, Egashira N, Mishima K, Hanna A, Yang J, Iwasaki K, Takahashi M, Fujiwara M, Ishiguro K, Bergeron C, Carlson GA, Abe K, Westaway D, St George-Hyslop P, Shoji M
  • Journal Title: Am J Pathol 169(4) Pages: 1365-1375
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enhanced accumulation of tau in double transgenic mice expressing mutant beta APP and presenilin-1. (2006)
  • Author(s): Samura E, Shoji M, Kawarabayashi T, Sasaki A, Matsubara E, Murakami T, Wuhua X, Tamura S, Ikeda M, Ishiguro K, Saido TC, Westaway D, St George Hyslop P, Harigaya Y, Abe K
  • Journal Title: Brain Res 1094(1) Pages: 192-199
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Type-specific evolution of amyloid plaque and angiopathy in APPsw mice. (2006)
  • Author(s): Harigaya Y, Tomidokoro Y, Ikeda M, Sasaki A, Kawarabayashi T, Matsubara E, Kanai M, Saido TC, Younkin SG, Shoji M.
  • Journal Title: Neurosci Lett 395(1) Pages: 37-41
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 老年期認知症ナビゲーター 第7章 生理・病理 (2006)
  • Author(s): 松原悦朗, 柳澤勝彦.
  • Journal Title: 老人斑,βアミロイド前駆体蛋白(APP)とβアミロイド (メディカルレビュー社)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cortical neuronal and glial pathology in Tg Taup301L transgenic mice : neuronal degeneration, memory disturbance, and phenotypic variation. (2006)
  • Author(s): Murakami T, Matsubara E, et al.
  • Journal Title: Am J Patrol 169 Pages: 1365-1375
• [Journal Article] Enhanced accumulation of tau in doubly transgenic mice expressing betaAPP and presenilin-1. (2006)
  • Author(s): Samura E, Matsubara E, et al.
  • Journal Title: Brain Res 1094 Pages: 192-199
• [Journal Article] Type-specific evolution of amyloid plaque and angiopathy in APPsw mice. (2006)
  • Author(s): Harigaya Y, Matsubara E, et al.
  • Journal Title: Neurosci Lett 395 Pages: 37-41
• [Journal Article] A unique case of limb-girdle muscular atrophy type 2A carrying novel compound heterozygous mutations in the human CAPN3 gene.
  • Author(s): Matsubara E et al.
  • Journal Title: Eur J Neurol (in press)
• [Presentation] アルツハイマー病におけるAβオリゴマー特異的受動免疫療法. (2008)
  • Author(s): 松原 悦朗
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Immunotherapy targetting Aβ oligomer for Alzheimer's disease. (2007)
  • Author(s): Matsubara E
  • Organizer: 第8回 アジア・オセアニア国際老年学会議
  • Place of Presentation: 北京
  • Year and Date: 2007-10-22
• [Book] 図説 分子病態学 4版(一瀬白帝, 鈴木宏治 編 著) (2008)
  • Author(s): 松原悦朗, 柳澤勝彦
  • Total Pages: 5
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 老年期認知症ナビゲーター 第7章 生理・病理 (2006)
  • Author(s): 松原悦朗, 柳澤勝彦.
  • Publisher: メディカルレビュー社
  • Description: 「研究成果報告書概要(欧文)」より
• [Patent(Industrial Property Rights)] Aβオリゴマーに特異的に結合する抗体およびその利用 (2007)
  • Inventor(s): 柴田昌夫,松原悦朗
  • Industrial Property Rights Holder: イムナス・ファーマ
  • Filing Date: 2007-10-19