It has been recently suggested that in Alzheimer disease (AD), the current available therapy with cholinesterase inhibitors (ChEIs) influences platelets amyloid precursor protein (APP) metabolism towards the nonamyloidogenic pathway. In order to investigate whether ChEIs may exert a protective role on vascular damage due to abeta deposition, several parameters of coagulation and fibrinolysis were assessed. Twenty patients with mild AD and 30 age-matched controls entered the study. All subjects performed a multidimensional neuropsychological assessment and a laboratory protocol. Individuals with vascular risk factors and systemic diseases were excluded. In mild AD patients, increased levels of markers of endothelial dysfunction, such as thrombomodulin (TM) and sE-selectin (sE-sel), were seen. After 1-month ChEIs treatment, a significant reduction of TM (p<0.05) and sE-sel (p<0.05) values towards the normal range was observed. These findings suggest that endothelial-related ChEIs action might contribute to the clinical efficacy in AD, slowing down pathology progression.