Importantly, the few studies published to this date on plasminogen activators and endothelial cells in AD indicate that although Aβ does not have an effect on the release of endothelial tPA [19], deficiency of this plasminogen activator, likely caused by increased PAI-1, underlies the impairment in neurovascular coupling observed in mice expressing the Swedish mutation of the amyloid precursor protein (APP; tg2576) [128]. This evidence concerns the gene APP and Alzheimer disease.