Development of a novel imaging biomarker of Abeta oligomers in the brain

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05228
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Oita University
• Principal Investigator: Matsubara Etsuro 大分大学, 医学部, 教授 (70219468)
• Co-Investigator(Kenkyū-buntansha): 松浦 栄次 岡山大学, 中性子医療研究センター, 教授 (20181688) ; 佐々木 崇了 岡山大学, 医歯薬学総合研究科, 助教 (10461253) ; 藪内 健一 大分大学, 医学部, 助教 (10763807) ; 三浦 由真子 大分大学, 医学部, 助教 (40761101)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Aβオリゴマー / 抗体 / PETイメジング / 画像バイオマーカー

Outline of Final Research Achievements

The aim of this study was to develop in vivo imaging biomarker for Aβ oligomers (AβOs) in the brain. Chelation of anti-AβO gave 89Zr-labelling efficiencies of more than 80%, resulted in ideal probe with preserved specificity almost identical to unlabeled antibody. Unfortunately, we did not make Aβ oligomers accumulation in the brain visible in vivo, whereas both ex vivo autoradiography and biodistribution study unequivocally revealed that brain uptake of 89Zr-labelled anti-AβO was significantly higher in APP-KI mice than in wild-type mice, indicating that the antibody can cross the blood-brain barrier. These findings indicated that further improvement of several factors (ex. BBB-penetrating activity, S/N ratio, and so on) is still necessary. However, 89Zr-labelled anti-ABO might be a potential candidate for in vivo imaging of AβO accumulation in the brain.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

本申請研究は、超高齢化社会を迎え介護予防推進が急務の我が国の介護の社会的負担の軽減が期待され、“アルツハイマー病は予防を標的とした先制医療対象疾患である”との概念導入に貢献しうる。さらに本研究は現状では治療法のない異常構造蛋白蓄積を伴う神経変性疾患にも普遍的な診断・治療として応用可能であり、神経変性疾患の全く新たな診断治療法開発に布石となる研究である。