The issues under discussion for this narrative review include: 1) the association of major peripheral lipoprotein subclasses, focusing on low-density lipoprotein (LDL) and high-density lipoprotein (HDL), on VCID and AD; 2) current challenges in using murine models to investigate mechanisms by which LDL and HDL contribute to VCID; and 3) describing the functions of cholesteryl ester transfer protein (CETP) in regulating the LDL:HDL ratio in humans, including therapeutic strategies targeting CETP. The gene discussed is CETP; the disease is Alzheimer disease.