Secreted from HIV-1-infected or HIV-transfected cells [24], Tat enters all CNS cells by endocytosis with the assistance of different receptors including low-density lipoprotein receptor-related protein 1 (LRP1), the major receptor for ApoE uptake in the brain; consequently, Tat is considered a key virulent factor of HIV-1 enhancing HIV infectivity and contributing to HIV/AIDS disease progression and the development of HAND [25–27]. The gene discussed is APOE; the disease is AIDS.