There are several ways for Aβ to be removed from the brain. Amyloid β can be directly shuttled out of the brain via protein complexes such as LRP1 and apolipoprotein E, which can bind extracellular Aβ and transport them to the blood brain barrier, where they are then shuttled to the other side [121]. Additionally, new observations suggest the existence of an alternate removal pathway, where extracellular Aβ in CNS interstitial fluid is moved into the cerebral spinal fluid in what is named the ‘glymphatic system’ [122]. Another way to clear Aβ is via phagocytosis and degradation by resident CNS immune cells, such as microglia [123], astrocytes [124], and possibly neurons [125]. This particular clearance pathway showcases the Janus face nature of microglia in that even though microglia are a primary source of inflammatory factors, they also represent a crucial element for removal of harmful material in the CNS [123]. Thus, the failure of microglia to carry out homeostatic functions possibly underscores one mechanism of increased Aβ accumulation during disease.
