APOE and Alzheimer disease: For instance, the major risk factor for Alzheimer's disease (AD) is the presence of the E4 isoform of apolipoprotein E, the major cholesterol transporter in the brain [2], while in Niemann-Pick type C (NPC) disease, mutations in the NPC1 and 2 proteins that affect intracellular cholesterol trafficking, are responsible for the pathology [3].