Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer's Disease Mice

Zhihong Bian, Xia Liu, Tian Feng, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Ryuta Morihara, Koji Abe, Toru Yamashita

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer's disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD+CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD+CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

Original languageEnglish
Pages (from-to)111-123
Number of pages13
JournalJournal of Alzheimer's Disease
Volume86
Issue number1
DOIs
Publication statusPublished - 2022

Keywords

  • Alzheimer's disease
  • cerebral amyloid angiopathy chronic cerebral hypoperfusion
  • rivaroxaban
  • warfarin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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