Though it remains unclear how apoE is involved in the pathogenesis of AD, it is of note that the levels of apoE4 are lower than those of apoE3 in the brain of apoE-targeted replacement (TR) mice expressing each of the human apoE isoforms under the control of the endogenous mouse promoter, and in the plasma and cerebrospinal fluid of humans with APOE3 or APOE4 [4,5,6,7]. Here, APOE is linked to Alzheimer disease.