Alzheimer's disease (AD) is a neurodegenerative disorder that leads to profound cognitive decline. The incidence of the disease is increasing and there are no effective treatments available, so new insights and therapies are sorely needed. Many AD patients suffer from altered cerebral blood flow, damaged cerebral vasculature, and abnormal hemostasis. Circulatory deficiencies could therefore play an important role in this disease. Recently, fibrinogen, the primary protein component of blood clots, has been identified as a strong cerebrovascular risk factor in AD. Fibrinogen specifically binds to the amyloid-beta (Abeta) peptide, altering fibrin clot structure and delaying clot degradation. We identified a novel inhibitor of this interaction using high throughput screening. Long-term treatment with this molecule significantly reduced AD pathology and improved cognition in mouse models of AD. These results suggest that inhibitors targeting the Abeta-fibrinogen interaction show promise as a therapy for AD. We are in the process of improving upon this molecule so that it is more potent and less toxic, strengthening the likelihood that it can be used in humans for AD treatment.