Proteomic profiling reveals age-related changes in transporter proteins in the human blood–brain barrier

Abstract

Abstract The Blood–Brain Barrier (BBB) is a selective barrier that regulates the entry of molecules including nutrients, environmental toxins, and therapeutic medications into the brain. Its function continues to evolve postnatally, through aging, and disease states. Here we present a global proteomics analysis focused on the ontogeny and aging of proteins in human brain microvessels (BMVs), predominantly composed of brain endothelial cells. Our proteomic study quantified 6,223 proteins and revealed possible age-related alterations in BBB permeability due to basement membrane component changes through the early developmental stage and age-dependent changes in transporter expression. Age dependent expression changes were observed within nutrient transporters and transporters that play critical roles in drug disposition. This research 1) provides important information on the mechanisms that drive changes in the metabolic content of the brain with age and 2) enables the creation of physiologically based pharmacokinetic models for CNS drug distribution across different life stages.