APOE and hyperlipidemia: Additionally, it was discovered that hypercholesterolemia significantly increased the expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9), BACE1, caspase-3, and Bax while only marginally increasing the expression of Bcl-2, suggesting that hyperlipidemia caused neuronal apoptosis in the hippocampus of apoE(/) mice via the Bcl-2/Bax–caspase-3 signaling pathway [51].