Even if APP is notoriously known for its contribution to pathogenesis of neurodegenerative diseases, and many physiological roles have been identified in neural cells (Perez et al., 1997; Nicolas and Hassan, 2014; Nhan et al., 2015; Habib et al., 2017; Coronel et al., 2018), little is known on its function on endothelial cells and cerebral vasculature (Figure 2). Here, APP is linked to neurodegenerative disease.