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

J Alzheimers Dis. 2022;86(1):111-123. doi: 10.3233/JAD-215318.

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.

Keywords: Alzheimer’s disease; cerebral amyloid angiopathy chronic cerebral hypoperfusion; rivaroxaban; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / therapeutic use
  • Animals
  • Anticoagulants / therapeutic use
  • Cerebral Amyloid Angiopathy* / drug therapy
  • Cerebral Amyloid Angiopathy* / pathology
  • Disease Models, Animal
  • Humans
  • Mice
  • Neuroinflammatory Diseases
  • Rivaroxaban / therapeutic use
  • Warfarin / therapeutic use

Substances

  • Amyloid beta-Peptides
  • Anticoagulants
  • Warfarin
  • Rivaroxaban