Given growing understanding of the regulatory role of apoE on microglia activation and characteristics in neurodegenerative disease and regulatory effect of human apoE isoforms on innate immune response [69, 71, 78] there is a strong premise to carry such studies in humans and in mice with targeted replacement of the murine Apoe gene for human APOE alleles [47]. The gene discussed is APOE; the disease is neurodegenerative disease.