“…As described above, P2Y 2 Rs mediate the Src-dependent transactivation of the vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells that promotes upregulation of monocyte-binding proteins (e.g., VCAM-1) and a decrease in endothelial adherens junction integrity [22,89,92,101,102]. Other studies have shown that microglia are attracted to and surround Aβ plaques in both human AD brain and rodent transgenic models that develop AD-like symptoms [228][229][230][231][232][233][234][235][236][237]. Although the role of microglial cells in AD (i.e., neurotoxic vs. neuroprotective) is controversial, recent work has shown that the majority of microglia that surround amyloid plaques in an AD mouse model are derived from monocytes originating in bone marrow [233,238] and thus must pass from the bone marrow into the bloodstream through the vasculature and across the BBB to reach sites of plaque formation in the brain.…”