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

## TL;DR

This study uses proteomic profiling to show how transporter proteins in the blood-brain barrier change with age, affecting brain metabolism and drug delivery.

## Contribution

The study identifies age-related changes in transporter proteins and their impact on BBB permeability and drug disposition.

## Key findings

- Age-related changes in basement membrane components affect BBB permeability during early development.
- Transporter expression changes with age, impacting nutrient and drug transport across the BBB.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-31224-6.