The role of neuroinflammation and responsible molecules in Alzheimer's disease onset

• Project/Area Number: 22790835
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: JI Bin 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (80392223)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: MCP-1 / Gila / TSPO / TSPO ligand / Alzheimer's disease / CCr2 / アミロイド / アルツハイマー病 / ミクログリア / 分子イメージング / PET / 神経炎症 / inflammation

Research Abstract

The present study have investigated the feasibility of anti-neuroinflammation therapy by positron emission tomography(PET) with amyloid and neuroinflammation tracers in Alzheimer's disease(AD). Here, an anti-MCP-1(Monocyte Chemotactic Protein-1) antibody was applied to anti-amyloid immunotherapy to verify whether anti-MCP-1 therapy is able to increase the therapeutic effect and attenuate the side-effect of anti-amyloid therapy. As results, co-administration of anti-MCP-1 and anti-A. antibodies have greatly increased the effect of anti-amyloid therapy and attenuated the occurrence of neuroinflammation compared the therapy with anti-A. antibody only in AD model APP23 mice expressing amyloid pathology.

Research Products

• [Journal Article] Mechanistic involvement of the calpain-calpastatin system in Alzheimer neuropathology (2012)
  • Author(s): Higuchi M, Iwata N, Matsuba Y, Takano J, Suemoto T, Maeda J, Ji B, Ono M, Staufenbiel M, Suhara T, Saido TC
  • Journal Title: FASEB J Volume: 26(3) Issue: 3 Pages: 1204-1217
  • DOI: 10.1096/fj.11-187740
  • Peer Reviewed
• [Journal Article] An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys : in vivo positron emission tomography imaging of glial activation (2012)
  • Author(s): Shimazawa, M., Ito, Y., Inokuchi, Y., Yamanaka, H., Nakanishi, T., Hayashi, T., Ji, B., Higuchi, M., Suhara, T., Imamura, K., Araie, M., Watanabe, Y., Onoe, H., and Hara, H.
  • Journal Title: PLoS One Volume: 7
• [Journal Article] PET Applications in Animal Models of Neurodegenerative and Neuroinflammatory Disorders (2012)
  • Author(s): Higuchi M, Maeda J, Ji B, Tokunaga M, Zhang MR, Maruyama M, Ono M, Fukumura T, Suhara T
  • Journal Title: Curr Top Behav Neurosci Volume: 11 Pages: 45-64
  • DOI: 10.1007/7854_2011_167
  • ISBN: 9783642287107, 9783642287114
  • Peer Reviewed
• [Journal Article] An Alteration in the Lateral Geniculate Nucleus of Experimental Glaucoma Monkeys : In vivo Positron Emission Tomography Imaging of Glial Activation (2012)
  • Author(s): Shimazawa M, Ito Y, Inokuchi Y, Yamanaka H, Nakanishi T Hayashi T, Bin Ji, Higuchi M, Suhara T, Imamura K, Araie M, Watanabe Y, Onoe H, Hara H
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] In vivo positron emission tomographic imaging of glial responses to amyloid-beta and tau pathologies in mouse models of Alzheimer's disease and related disorders (2011)
  • Author(s): Maeda J, Zhang MR, Okauchi T, Ji B, Ono M, Hattori S, Kumata K, Iwata N, Saido TC, Trojanowski JQ, Lee VM, Staufenbiel M, Tomiyama T, Mori H, Fukumura T, Suhara T, Higuchi M
  • Journal Title: J Neurosci. Volume: 31(12) Issue: 12 Pages: 4720-4730
  • DOI: 10.1523/jneurosci.3076-10.2011
  • Peer Reviewed
• [Journal Article] 認知症の分子イメージング (2011)
  • Author(s): 須原哲也,樋口真人,前田純,季斌
  • Journal Title: 生物学的精神医学会誌 Volume: 21巻4号 Pages: 261-266
  • NAID: 10029785231
• [Journal Article] アルツハイマー病のホールマークと神経炎症の分子イメージング (2011)
  • Author(s): 季斌、樋口真人、須原哲也
  • Journal Title: 最新医学 Volume: 66巻10号 Pages: 77-83
• [Journal Article] 認知症の分子イメージング (2011)
  • Author(s): 須原哲也, 樋口真人, 前田純, 季斌
  • Journal Title: 生物学的精神医学会誌 Volume: 21 Pages: 261-266
  • NAID: 10029785231
• [Journal Article] In Vivo Positron Emission Tomographic Imaging of Glial Responses to Amyloid-b and Tau Pathologies in Mouse Models of Alzheimer's Disease and Related Disorders (2011)
  • Author(s): Maeda J, Zhang MR, Okauchi T, Bin Ji, Ono M, Hattori S, Kumata K, Iwata N, Saido TC, Trojanowski JQ, Lee VM, Staufenbiel M, Tomiyama T, Mori H, Fukumura T, Suhara T, Higuchi M.
  • Journal Title: Journal of Neuroscience Volume: 12 Pages: 4720-30
  • Peer Reviewed
• [Journal Article] In-vivo visualization of key molecular processes involved in Alzheimer's disease pathogenesis : Insights from neuroimaging research in humans and rodent models (2010)
  • Author(s): Higuchi, M., Maeda, J., Ji, B., Maruyama, M., Okauchi, T., Tokunaga, M., Ono, M., and Suhara, T
  • Journal Title: Biochim Biophys Acta Volume: 1802 Issue: 4 Pages: 373-388
  • DOI: 10.1016/j.bbadis.2010.01.003
• [Journal Article] アルツハイマー病の分子イメージング (2010)
  • Author(s): 季斌、樋口真人、須原哲也
  • Journal Title: Pharma Medica Volume: 28巻7号 Pages: 39-43
• [Journal Article] In-vivo visualization of key molecular processes involved in Alzheimer's disease pathogenesis : Insights from neuroimaging research in humans and rodent models (2010)
  • Author(s): Higuchi M, Maeda J, Bin Ji, Maruyama M, Okauchi T, Tokunaga M, Ono M, Suhara T
  • Journal Title: Biochim Biophys Acta. Volume: 1802 Pages: 373-88
  • Peer Reviewed
• [Presentation] 神経変性疾患における神経炎症のPETイメージング (2011)
  • Author(s): 季斌、樋口真人、須原哲也
  • Organizer: 第23回日本脳循環代謝学会総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-11-04
• [Presentation] Molecular imaging for neuroinflammation (2011)
  • Author(s): 季斌
  • Organizer: 第34回日本神経科学大会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-17
• [Presentation] In vivo imaging and therapeutic modulations of microglial response to A-beta amyloidosis by interrupting deleterious chemokine signaling in a rodent model of Alzheimer's disease (2010)
  • Author(s): Bin Ji, Maruyama M, Hattori S., Maeda J., Ono M., Okauchi T., Zhang MR., Higuchi M., Suhara T
  • Organizer: 第29回内藤コンファレンス
  • Place of Presentation: 神奈川県三浦郡
  • Year and Date: 2010-10-07