FIGURE 1.

Initially, defects in Aβ clearance pathways lead to accumulation of the peptide in the brain leading to neuronal toxicity. Activated microglial cells are capable of performing several macrophage-like immune functions, such as cytokine release and phagocytosis of Aβ. However, exhausted microglia are a common signature in AD. Majority of AD patients suffer from cerebrovascular dysfunction, which compromises the integrity of the blood-brain barrier (BBB). A compromised BBB promotes the entry of infiltrating cells within the perivascular space and brain parenchyma and infiltrating cells may exacerbate or alleviate disease progression. Mononuclear phagocytic cells can enter and become involved in CNS pathological situations. Under pathophysiological conditions, Ly6C^high monocytes adhere to brain endothelium and consequently infiltrate brain parenchyma. Ly6C^low monocyte subset associates with Aβ-positive veins, but not arteries, internalizes Aβ, and efficiently eliminates Aβ microaggregates and transports them from the brain microvasculature to the blood circulation.