2013 Fiscal Year Final Research Report
Study for the metabolism and neurotoxicity of amyloid beta peptide oligomers
| Project/Area Number |
24800015
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | 脳神経疾患 / 神経科学 / アルツハイマー病 / アミロイドβタンパク質 / アポリポプロテインE |
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| Research Abstract |
To elucidate the mechanism of the metabolism of amyloid beta peptide (Abeta) oligomers in the brain, we have developed in vivo microdialysis technique using a 1,000 kDa cut-off microdialysis probe. Using this techqnique, we identified that the clearance rate of Abeta in the brain of plaque-bearing APP transgenic mice was significantly slower than that in the brain of plaque-free APP transgenic mice. We also identified that the level of ISF Abeta in the brain of APP / CLAC double transgenic mice was significantly lower than that of APP transgenic mice. These observations suggested that amyloid plaque affect the metabolism of Abeta monomer and oligomers in the brain. We have also developed an easy and high-sensitive method to evaluate the interaction between Abeta and apoE using a plit-luciferase complementation assay.
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[Journal Article] Human ApoE isoforms delivered via gene transfer differentially modulate Alzheimer's disease by affecting amyloid deposition, clearance, and neurotoxicity2013
Author(s)
Eloise Hudry, Jonathan Dashkoff, Allyson Lee, Shuko Takeda, Robert M. Koffie, Tadafumi Hashimoto, Maria Scheel, Tara Spires-Jones, Michal Arbel-Ornath, Rebecca Betensky, Beverly L Davidson, and Bradley T Hyman
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Journal Title
Sci. Trans. Med.
Volume: 5(212)
Pages: 212ra161
DOI
Peer Reviewed
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[Journal Article] RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy2013
Author(s)
Ryoko Ihara, Koji Matsukawa, Yusei Nagata, Hayato Kunugi, Shoji Tsuji, Takahiro Chihara, Erina Kuranaga, Masayuki Miura, Tomoko Wakabayashi, Tadafumi Hashimoto, and Takeshi Iwatsubo
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Journal Title
Hum. Mol. Genet.
Volume: 22
Pages: 4474-4484
DOI
Peer Reviewed
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[Journal Article] Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid beta peptide2012
Author(s)
Tadafumi Hashimoto, Alberto Serrano-Pozo, Yukiko Hori Kenneth W Adams, Shuko Takeda, Adrian O Banerji, Akinori Mitani, Daniel Joyner, Diana H Thyssen, Brian J Bacskai, Matthew P Frosch, Tara L Spires-Jones, Mary Beth Finn, David M Holtzman, and Bradley T Hyman
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Journal Title
J. Neurosci.
Volume: 32
Pages: 15181-15192
DOI
Peer Reviewed
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[Presentation] Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid beta peptide. Gordon Research Conferences, Neurobiology of brain disorders2012
Author(s)
Tadafumi Hashimoto, Alberto Serrano-Pozo, Yukiko Hori, Hwan-Ching Tai, Kenneth W Adams, Shuko Takeda, Daniel Joyner, Diana H Thyssen, Brian J Bacskai, Matthew P Frosch, Tara L Spires-Jones, Mary Beth Finn, David M Holtzman, and Bradley T Hyman
Organizer
Neurobiology of brain disorders
Place of Presentation
Easton, USA.
Year and Date
20120800
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[Presentation] Remodeling of the morphology of beta-amyloid plaques by CLAC in the brains of transgenic mice2012
Author(s)
Tadafumi Hashimoto, Daisuke Fujii, Mayu Kashiwagi, Yuko Matsuo, Yusuke Matsura, Tomoko Sakakura, Hisatomo Kowa, David Westaway, Tomoko Wakabayashi, and Takeshi Iwatsubo
Organizer
Society for Neuroscience
Place of Presentation
New Oreleans, USA.
Year and Date
2012-10-15
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