Fig. 2.

Essential Aβ clearance vascular and other routes. Aβ clearance can occur via several routes: 1 LRP-mediated transcytosis (purple, receptor) across the blood–brain barrier (red, capillaries) removes Aβ from brain interstitial fluid to blood and LRP-mediated degradation of Aβ on vascular smooth muscle cells and pericytes lowers Aβ levels in perivascular spaces (blue, cells), 2 soluble LRP, sLRP-mediated (purple, soluble receptor) endogenous Aβ “sink” action in plasma increases peripheral Aβ clearance and lowers the levels of free Aβ in the circulation which in turn promotes the cell surface LRP-mediated clearance of brain-derived Aβ across the blood–brain barrier, 3 Aβ chaperones in brain interstitial fluid such as ApoE isoforms may reduce clearance of brain-derived Aβ in an isoform-specific manner, i.e., apoE4 > apoE3 or apoE2, 4 clearance of Aβ by microglia and perivascular brain macrophages (orange, cells) from brain parenchyma and perivascular spaces, respectively, 5 direct enzymatic degradation of Aβ in the brain (green, enzymes), and 6 elimination of Aβ along the perivascular spaces by passive drainage that is influenced by the arterial pulstatile flow. The illustrated pathways by all means do not cover in detail all possible routes that control Aβ levels in the brain