Figure 1.

Peripheral and central sources of ApoE. In peripheral tissues, ApoE is expressed primarily by the liver and released into the blood. In the brain, ApoE is expressed primarily by astrocytes, but can also be expressed by neurons and microglia during cell stress or injury (Pitas et al., 1987; Stone et al., 1997; Xu et al., 2008). Typically, ApoE cannot pass through the BBB (Björkhem et al., 1998); thus, the two pools of ApoE are largely separate. In ApoE knock-out mice, the lack of peripheral ApoE leads to a catastrophic increase of lipoprotein particles (Sheng et al., 1998). To study the effect of ApoE loss on synaptic loss in the presence of normal plasma lipids, we have developed an ApoE “brain knockout” (bEKO mice), which has normalized the peripheral ApoE level.