PICALM and Alzheimer disease: For example, we found lower expression of PICALM in EC with AD, suggesting that two complementary mechanisms by which vascular clearance of Αβ is reduced in the disease35,51 are linked: downregulation of PICALM lowering efflux of Aβ and downregulation of angiogenic VEGF-VEGFR, TGFβ and semaphorin signalling pathways reducing the functional vascular density74,75.