Imaging neurofibrillary tangles and astrogliosis for the clarification of the pathogenesis of Alzheimer's disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H02771
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Okamura Nobuyuki 東北医科薬科大学, 医学部, 教授 (40361076)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: アルツハイマー病 / 神経炎症 / アストログリオーシス / イメージング / アミロイド / タウ / モノアミン酸化酵素 / PET

Outline of Final Research Achievements

[18F]SMBT-1 was successfully developed for in vivo imaging of reactive astrogliosis in the human brain. In the clinical study, [18F]SMBT-1 PET showed positive findings not only in patients with Alzheimer's disease but also in amyloid-positive cognitively normal elderly. These findings suggest that the proliferation of reactive astrocytes is an early event that is closely associated with amyloid-beta accumulation in Alzheimer's disease continuum.
We further developed a novel tau PET probe, [18F]SNFT-1. [18F]SNFT-1 showed high binding affinity and selectivity for tau aggregates in Alzheimer's disease brains, suggesting the potential usefulness for in vivo detection of early tau pathology.

Free Research Field

薬理学、核医学

Academic Significance and Societal Importance of the Research Achievements

[18F]SMBT-1 PETは、アルツハイマー病の病初期から発生する神経炎症（反応性アストログリオーシス）を生体脳において優れた感度で検出できることが証明され、今後、多様な神経疾患における神経炎症の把握や、新規治療薬開発におけるバイオマーカーとしての活用が期待できる。新規タウPETプローブ[18F]SNFT-1は既存のタウPETプローブよりも高い感度で、アルツハイマー病の初期タウ病理を描出できる可能性が本研究結果から示唆され、今後の臨床研究の成果が期待される。