The brain's cholesterol system operates almost entirely independently from the body's peripheral system, using apoE-containing lipoproteins instead of apoB particles. Understanding this distinction is critical for evaluating how statins, ezetimibe, omega-3s, and emerging CETP inhibitors affect brain health, Alzheimer's risk, and whether lowering peripheral cholesterol harms cognition—a widespread misconception. The brain synthesizes and stores 20-25 grams of cholesterol—20 times more than the liver—primarily in myelin and neuronal membranes, with production beginning in utero and continuing independently of circulating blood cholesterol.