Transport of drugs across the blood–brain barrier in Alzheimer’s disease

Abstract

Alzheimer’s disease, a neurodegenerative disorder, is associated with various pathological alterations to the blood–brain barrier, including disruption to the inter-endothelial tight junction proteins, altered expression of transport proteins involved in drug efflux, a reduction in cerebral blood flow and a thickening of the brain capillary basement membrane. There are many conflicting reports on whether such changes alter the ability of endogenous proteins to extravasate into the brain parenchyma, and there are even fewer reports focusing on the potential impact of these changes on drug transport into the CNS. The purpose of this review is to critically evaluate how the reported changes to the blood–brain barrier in Alzheimer’s disease have (or have not) resulted in altered CNS drug delivery, and to highlight the requirement for more rigorous and systematic studies in this field for the benefit of drug discovery and delivery scientists.