Challenge for neutralizing antibody theory: Vaccine development specific to Abeta oligomers

• Project/Area Number: 25670415
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Oita University
• Principal Investigator: ETSURO Matsubara 大分大学, 医学部, 教授 (70219468)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ワクチン / 抗体 / Aβ重合体 / アルツハイマー型認知症

Outline of Final Research Achievements

It has been well known that Aβ oligomers are synaptotoxic and molecular basis of memory loss, which is candidate molecules for drug development in Alzheimer’s disease. We aimed to develop a novel vaccine targeting Aβ oligomers alone to assess if the appearance of neutralizing antibody against parent one is really problematic or not from therapeutic point of view. It was easy to make neutralizaing antibodies. However, when anti-ideotype antibodies themselves were directly immunized to mouse pad, we can hardly detect anti-ideotypic antibodies in blood obtained from immunized mice, suggesting that we need to design something like anti-ideotype vaccine to retrieve of in vivo action.

Research Products

• [Journal Article] Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice. (2014)
  • Author(s): Pappolla M, Sambamurti K, Vidal R, Pacheco-Quinto J, Poeggeler B, Matsubara E
  • Journal Title: Neurobiol Dis Volume: 71C Pages: 215-219
  • DOI: 10.1016/j.nbd.2014.07.012
  • Peer Reviewed / Open Access
• [Journal Article] Lack of genetic association between TREM2 and late-onset Alzheimer’s disease in a Japanese population (2014)
  • Author(s): Akinori Miyashitaa, Yanan Wen 他
  • Journal Title: J Alzheimer's Dis. Volume: 印刷中 Issue: 4 Pages: 1301-1308
  • DOI: 10.3233/jad-140225
  • Peer Reviewed / Open Access
• [Journal Article] SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians (2013)
  • Author(s): Miyashita A, Koike A, Jun G, Kawarabayashi T, Shoji M,Arai H, Asada T, Harigaya Y, Ikeda M, Amari M, Ikeuchi T, St. George-Hyslop P,
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e58618-e58618
  • DOI: 10.1371/journal.pone.0058618
  • Peer Reviewed
• [Journal Article] Disease Modifying Therapies for Alzheimer's disease targeting Aβ oligomers: Implications for therapeutic mechanisms (2013)
  • Author(s): Matsubara E, Takamura A, Okamoto Y, Oono H, Nakata T, Wakasaya W, Kawarabaayshi T, Shoji M
  • Journal Title: BioMed Res Int Volume: 2013 Pages: 1-6
  • DOI: 10.1155/2013/984041
  • Peer Reviewed
• [Presentation] 予防的創薬の現状 (2014)
  • Author(s): 松原 悦朗
  • Organizer: 第２６回日本脳循環代謝学会総会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
  • Year and Date: 2014-11-22
  • Invited
• [Book] 新しい診断と治療のABC２２ アルツハイマー型認知症 改訂第２版 神経３ (2014)
  • Author(s): 松原 悦朗
  • Total Pages: 224
  • Publisher: 最新医学社