Direct thrombin inhibitors' potential efficacy in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease with no available disease-modifying drugs. However, it has been postulated that neurovascular damage is a primary occurrence in this disease. Neurovascular damage is the result of the presence of cardiovascular risk factor generating hypoxia, oxidative stress, and metabolic changes that activate the endothelial cells of the brain microvasculature in order to respond to the stress by the development of angiogenesis. This endothelial activation could lead to a secretion of many proinflammatory cytokines and growth factors, such as thrombin. Heparin and related oligosaccharides have been shown to be efficient in the improvement of symptoms of AD. Their efficacy may be limited by their nonselective inhibitory effect of thrombin's activity. Direct thrombin inhibitors, such as dabigatran, might be efficient in the treatment of patients with AD because of their high selectivity for thrombin's activity inhibition while having a safer side effects profile than heparin.