PGP and early-onset autosomal dominant Alzheimer disease: Located on the luminal and abluminal membrane surface of brain microvascular endothelium [6], P-gp's vast substrate profile renders it a formidable obstacle for effective drug delivery to the brain and efficacious treatment of CNS and non-CNS disorders such as epilepsy, HIV-1 encephalitis, Alzheimer's disease, and peripheral inflammatory pain (PIP) [7]–[10].