Figure 4. . A working model that links cholesterol trafficking with ACAT1, 24S-hydroxycholesterol biosynthesis and downregulations of human APP and HMG-CoA reductase in neurons.

This model predicts that ACAT1 blockage provides more cholesterol as substrate for the enzyme CYP46A1 to synthesize more 24S-hydroxycholesterol. The increase in cholesterol and in 24S-hydroxycholesterol at the ER serve as the signal(s) to downregulate the protein contents of hAPP and HMGR.

ACAT1: Acyl-CoA:cholesterol acyltransferase 1; ER: Endoplasmic reticulum; hAPP: Human APP.