The societal burden of Alzheimer's disease (AD), a neurodegenerative dementing disorder, is staggering. Current estimates suggest that 5.4 million Americans and 36 million people worldwide have AD. There are currently no disease-modifying treatments for AD. Identification of new therapeutic targets is a critical barrier to progress in the AD field. Research in AD has been dominated by one hypothesis focused on a single protein. It is clear that AD is a complex disorder and that multiple underlying processes contribute to disease progression. Our lab has worked for almost 30 years to understand how brain blood vessels may be involved in AD. We were the first to show in human AD that brain blood vessels are dysfunctional and a source of inflammatory proteins, a process we term vascular "activation". We recently showed in AD animal models similar brain blood vessel activation. It is our novel idea that brain vascular activation is an important contributor to the injury and eventual death of brain nerve cells in AD and possibly an unexplored therapeutic target. We have tested the idea that inhibiting brain blood vessel activation is beneficial in AD in animals and have encouraging data that show this approach significantly improves memory. Although many studies where AD was "cured" in animals have not led to success in humans, because we discovered vascular activation in humans, and then further confirmed its importance and validated it as a target in animal models, we believe our proposal to now test this idea in humans is sound. In the current project we propose to take the first step toward defining this new previously untested area of AD treatments. We propose a pilot phase I clinical trial to test the safety and tolerability of a drug (dabigatran) which blocks a key protein that controls vascular activation.