Relevance of chronic kidney disease with tau pathology onset in the Alzheimer's disease mouse model

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20688
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Nagoya City University
• Principal Investigator: Manabe Tatsuya 名古屋市立大学, 医薬学総合研究院(医学), 助教 (60944006)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: タウ / 慢性腎臓病 / アルツハイマー病

Outline of Final Research Achievements

Development of mouse models recapitulating all the Alzheimer’s disease (AD) pathological hallmarks is essential for discovering effective treatments. Due to the lack of tau pathology in the currently available mouse models, AD pathogenesis remains largely unknown. We hypothesised that mice may not express sufficient tau levels in the brain for tau pathogenesis and tested whether chronic kidney disease (CKD) could elevate the total tau levels in the brain. To this end, we induced CKD in aged mice and found a rise in tau phosphorylation with total tau levels unchanged. Our findings suggested that CKD could worsen AD pathology by promoting tau phosphorylation and its subsequent aggregation in the brain.

Free Research Field

神経病態学

Academic Significance and Societal Importance of the Research Achievements

CKDは加齢性疾患であり、孤発性AD患者の一部でその併存が知られている。タウに関連したAD―CKDの病態類似性について臨床報告が相次いでいるが、未だマウスモデルを用いた検証はなされていない現状であった。本研究では初めてCKDという慢性的な疾患がADなどの神経変性疾患に深く関連する脳のタウに影響を及ぼした上で、学術的な意義は高い。そして、AD―CKDという疾患連関研究は独自性の高い研究課題であり、臨床的にも重要な示唆を提供するとともに、ADモデル開発の向上にも深い洞察を提供する研究である。