Cerebrovascular-oriented combined cerebral amyloid angiopathy eradication therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 19KK0410
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kumamoto University
• Principal Investigator: Inoue Yasuteru 熊本大学, 大学院生命科学研究部(医), 特定研究員 (00806408)
• Project Period (FY): 2020 – 2023
• Keywords: 脳アミロイド血管症 / アミロイドβ / アミロイドーシス

Outline of Final Research Achievements

The applicant developed a model to continuously administer α-enolase (ENO1) into the brain of CAA/AD transgenic mice using an infusion pump. They conducted biochemical and behavioral analyses, finding that ENO1 reduced amyloid-beta (Aβ) deposition in the brain vasculature and parenchyma, with significant decreases in insoluble Aβ40 and Aβ42. Spatial working memory improved in the ENO1-treated group. ENO1 likely inhibits Aβ polymerization, as evidenced by reduced Aβ monomers. There were no differences in amyloid precursor protein (APP) or its metabolites between treated and untreated groups. ENO1 was nitrosylated in CAA/AD mice, reducing its enzymatic activity in vitro. Heat-inactivated ENO1 did not reduce Aβ or improve memory, suggesting that nitrosylation decreases ENO1 activity, contributing to CAA/AD progression.

Free Research Field

脳神経科学

Academic Significance and Societal Importance of the Research Achievements

申請者は、α-エノラーゼ（ENO1）を使い、脳内にアミロイドベータ（Aβ）が蓄積するアルツハイマー病モデルマウスで研究を行いました。ENO1を脳に持続投与すると、Aβの蓄積が減少し、記憶機能が改善されました。これにより、ENO1がAβの分解を助け、アルツハイマー病の進行を遅らせる可能性が示されました。社会的には、アルツハイマー病の新しい治療法開発に貢献する重要な研究成果です。