RU-505 is an inhibitor of the interaction between amyloid-β (Aβ) and fibrinogen, with a higher efficacy for inhibiting monomeric forms of Aβ bound to fibrinogen over oligomeric forms. In vitro, RU-505 (20 μM) normalizes fibrin clot formation that is disrupted when fibrinogen is bound to Aβ42. RU-505 (35 mg/kg) decreases the incidence of vessel occlusion in the Tg6799 transgenic mouse model of Alzheimer’s disease. Chronic treatment with RU-505 (35 mg/kg, s.c., every other day for 3 months) decreases Aβ deposition in blood vessels and cortical fibrinogen infiltration and microgliosis in the brain of Tg6799 mice. In addition, it improves spatial memory in chronically treated Tg6799 mice compared with vehicle control mice.
