Figure 9. ApoE and its lipidation status regulates the proteolytic degradation of soluble Aβ.
The level of soluble Aβ is homeostatically controlled by its production by neurons and its subsequent clearance. Soluble Aβ can be cleared by proteolytic enzymes including NEP and IDE acting both intracellularly and extracellularly. ApoE is principally synthesized and secreted by glia. The lipid transporter ABCA1 mediates the lipidation of ApoE. Liver X receptors regulate the expression of both ABCA1 and ApoE and their activation results in increased levels of lipidated ApoE. The degradation of soluble Aβ both intracellularly and extracellularly is enhanced by increasing ApoE and its lipidation.