Figure 4

Elimination of amyloid-beta (Aβ) from the brain. Aβ is (i) produced by neurons and other cells in the brain and then (ii) diffuses with interstitial fluid and other solutes through the narrow extracellular spaces (ECS) of the brain to (iii) the bulk flow lymphatic drainage pathways in the basement membranes of capillaries and in the tunica media of artery walls and (iv) out of the brain to cervical lymph nodes. Smooth muscle cells and perivascular macrophages take up Aβ and are part of the elimination pathway. Degradation of Aβ occurs in the brain parenchyma, by neprilysin and other enzymes, and Aβ is absorbed into the blood by LRP-1 (lipoprotein receptor-related protein-1)-mediated mechanisms in capillary endothelia. These mechanisms for the elimination of Aβ from the brain tend to fail with age and in Alzheimer disease.