Development of diagnostic and therapeutic agents targeting neuro fibrillary tangles in Alzheimer's disease.

• Project/Area Number: 19790846
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: MARUYAMA Masahiro National Institute of Radiological Sciences, 分子イメージング研究センター, 主任研究員 (80396481)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,570,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: 神経原線維変化 / micro PET scan / 蛍光イメージング / 神経源線維変化

Research Abstract

タウオパチーモデルマウスの神経原線維変化に特異的に結合する蛍光プローブをスクリーニングした。選定した蛍光プローブと蛍光イメージング装置を用いてマウスの神経原線維変化を生体レベルで観察することに成功した。そして病変量の変動をモニターするためにポジトロン断層撮影(positron emission tomography; PET)用プローブを開発し、microPET scanを行った。神経原線維変化を標的とした画像バイオマーカーとして利用できることが明らかとなった。

Research Products

• [Journal Article] In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease (2008)
  • Author(s): Okamura N, Funaki Y, Tashiro M, Kato M, Ishikawa Y, Maruyama M, Ishikawa H, Meguro K, Iwata R, Yanai K
  • Journal Title: Br J Clin Pharmacol. 65(4) Pages: 472-9
  • Peer Reviewed
• [Journal Article] Effects of a sedative antihistamine, D-chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving (2008)
  • Author(s): Tashiro M, Sakurada Y, Mochizuki H, Horikawa E, Maruyama M, Okamura N, Watanuki S, Arai H, Itoh M, Yanai K
  • Journal Title: Hum Psychopharmacol. 23(2) Pages: 139-50
  • Peer Reviewed
• [Journal Article] In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease. (2008)
  • Author(s): Okamura N, Funaki Y, Tashiro M, Kato M, Ishikawa Y, Maruyama M, Ishikawa H, Meguro K, Iwata R, Yanai K.
  • Journal Title: Br J Clin Pharmacol. 65 Pages: 472-9
  • Peer Reviewed
• [Journal Article] A transient increase in cerebrospinal fluid tau level after epileptic seizure in an elderly patient (2007)
  • Author(s): Matsui T, Maruyama M, Matsushita S, Arai H, Higuchi S, Maruyama K
  • Journal Title: J Am Geriatr Soc. 55(12) Pages: 2096-7
  • Peer Reviewed
• [Journal Article] Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography (2007)
  • Author(s): Maeda J, Ji B, Irie T, Tomiyama T, Maruyama M, Okauchi T, Staufenbiel M, Iwata N, Ono M, Saido TC, Suzuki K, Mori H, Higuchi M, Suhara T
  • Journal Title: J Neurosci. 27(41) Pages: 10957-68
  • Peer Reviewed
• [Journal Article] 2-(2-[2-Dimethylaminothiazol-5-yl]ethenyl)-6- (2-[fluoro]ethoxy)benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer's disease patients (2007)
  • Author(s): Kudo Y, Okamura N, Furumoto S, Tashiro M, Furukawa K, Maruyama M, Itoh M, Iwata R, Yanai K, Arai H
  • Journal Title: J Nucl Med. 48(4) Pages: 553-61
  • Peer Reviewed
• [Journal Article] 2-(2-[2-Dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy) benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer's disease patients. (2007)
  • Author(s): Kudo Y, Okamura N, Furumoto S, Tashiro M, Furukawa K, Maruyama M, Itoh M, Iwata R, Yanai K, Arai H.
  • Journal Title: J Nucl Med. 48 Pages: 553-61
  • Peer Reviewed
• [Journal Article] Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography. (2007)
  • Author(s): Maeda J, Ji B, Irie T, Tomiyama T, Maruvama M, Okauchi T, Staufenbiel M, Iwata N, Ono M, Saido TC, Suzuki K, Mori H, Higuchi M, Suhara T.
  • Journal Title: J Neurosci. 27 Pages: 10957-68
  • Peer Reviewed
• [Journal Article] A transient increase in cerebrospinal fluid tau level after epileptic seizure in an elderly patient. (2007)
  • Author(s): Matsui T, Maruyama M, Matsushita S, Arai H, Higuchi S, Mareyama K.
  • Journal Title: J Am Geriatr Soc. 55 Pages: 2096-7
  • Peer Reviewed
• [Journal Article] Effects of a sedative antihistamine, D-chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving. (2007)
  • Author(s): Tashiro M, Sakurada Y, Mochizuki H, Horikawa E, Maruyama M, Okamura N, Watanuki S, Arai H, Itoh M, Yanai K.
  • Journal Title: Hum Psychopharmacol. 23 Pages: 139-50
  • Peer Reviewed