Development of imaging-based diagnostic procedures for brain protein aging

2018 Fiscal Year Final Research Report

• Project Area: Prevention of brain protein aging and dementia
• Project/Area Number: 26117008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Sahara Naruhiko 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, グループリーダー(定常) (40261185)
• Co-Investigator(Kenkyū-buntansha): 山口 芳樹 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (90323451)
• Research Collaborator: Higuchi Makoto ; Matsumoto Gen ; Minamimoto Takafumi ; Aoki Ichio
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: タウ / 脳イメージング / タウオパチー / マウスモデル

Outline of Final Research Achievements

Aims of this project are to develop biomarkers and to establish diagnostic procedures for brain protein aging. During past 5 years, rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging. PET studies with [11C]PBB3 and [11C]AC-5216 tracers, which labeled tau pathology and TSPO, revealed age-dependent increases, and correlated with age-dependent volume reduction in the forebrain on MRI. Histochemical analyses confirmed the relevance of pathological tau accumulation and elevated TSPO immunoreactivity in putative microglia. Our results indicate that in vivo imaging of animal models is able to explore the temporospatial relationship among tau deposition, neuroinflammation and neuronal loss. Non-invasive PET imaging combined with transgenic mouse models can be a powerful experimental tool to investigate mechanisms of neurodegenerative diseases and evaluate therapeutic interventions.

Free Research Field

神経化学、認知症学

Academic Significance and Societal Importance of the Research Achievements

多くの神経変性疾患では脳内に不要なタンパク質の沈着物が出現する。老化に伴い不要なタンパク質の沈着が増大することから、これらタンパク質の沈着が疾患の発症原因ではないかと考えられてきた。本研究では、疾患動物モデルにPET, MRIなどの生体イメージング技術を適用し、病態進行度を評価しうる実験系を確立した。今後、認知症の根本治療薬の評価系として活用されることが期待できる。