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

Article type: Research Article

Authors: Bian, Zhihong^a | Liu, Xia^a | Feng, Tian^a | Yu, Haibo^a | Hu, Xiao^a | Hu, Xinran^a | Bian, Yuting^a | Sun, Hongming^a | Tadokoro, Koh^a | Takemoto, Mami^a | Yunoki, Taijun^a | Nakano, Yumiko^a | Fukui, Yusuke^a | Morihara, Ryuta^a | Abe, Koji^b | Yamashita, Toru^{a; *}

Affiliations: [a] Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan | [b] National Center Hospital, National Center of Neurology and Psychiatry, Kodaira-shi, Tokyo, Japan

Correspondence: [*] Correspondence to: Dr. Toru Yamashita, Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Tel.: +81 86 235 7365; Fax: +81 86 235 7368; E-mail: [email protected].

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

DOI: 10.3233/JAD-215318

Journal: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 111-123, 2022