In line with this, it has been demonstrated that a deficiency in this transporter in transgenic mice overexpressing human APP can exacerbate neurovascular dysfunction in AD by generating a series of parallel pathogenic mechanisms in the cerebral microcirculation, namely, a significant reduction in the expression of tight junctions, capillary degeneration, neurovascular uncoupling, BBB breakdown, decreased brain perfusion and impaired Aβ clearance (Winkler et al., 2015). This evidence concerns the gene APP and Alzheimer disease.