Fig. (9) Cholesterol and APP processing. Cholesterol plays a central role in APP metabolism and Aβ synthesis. APP metabolism starts in the ER and then enters the Golgi complex and the plasma membrane. In the plasma membrane, Aβ is released from APP. The free Aβ binds with membrane-associated cholesterol, ultimately resulting in Aβ aggregation. The remaining free Aβ binds with ApoE and the cholesterol complex to re-enter the cell through the LRP receptor system. This ApoE-Aβ complex is degraded by lysosome enzymes to release the free cholesterol and Aβ.