Protective Effects of Rivaroxaban on White Matter Integrity and Remyelination in a Mouse Model of Alzheimer’s Disease Combined with Cerebral Hypoperfusion

Abstract

Background: Alzheimer’s disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear. Objective: The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice. Methods: In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter. Results: The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss. Conclusions: These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia.