Clearance of beta-amyloid in the brain.

Intravascular substances invade extracellular spaces in the brain via endothelial cells in the sites without bloodbrain barrier (BBB) and move not only in the cerebrospinal fluid (CSF) but also in the interstitial fluid (ISF) of brain parenchyma adjacent to non-BBB sites. It is likely that CSF drains directly into the blood via arachnoid villi and granulations and also to lymph nodes via subarachnoid spaces in the brain and nasal lymphatics, whereas ISF drains to cervical lymph nodes through pathways along vascular wall of capillaries and arteries. As the supposed pathways of fluids seem to be critical for the maintenance of normal brain function, it is reasonable to suspect that an obstacle to the passage of fluids through these pathways likely induces some kinds of brain dysfunction such as Alzheimer's disease. According to assumed pathways for the elimination of amyloid-β (Aβ) from the brain, Aβ peptides produced mainly in neurons are degraded by peptidases, flow out of the brain parenchyma into the blood through efflux transporters located in cerebral vessels, drain through perivascular pathways into the cervical lymph nodes, or are taken up by some kinds of cells in the brain. As for the perivascular pathways, ISF including Aβ peptides diffuses in the extracellular spaces of the brain parenchyma, enters basement membranes of capillaries, passes into the tunica media of arteries, and drains out of the brain. In this review, these pathways for the clearance of fluids including Aβ from the brain into the blood are briefly reviewed and the relationship between dysfunction of these pathways and brain diseases is discussed.