P-Glycoprotein Function at the Blood–Brain Barrier: Effects of Age and Gender

Abstract

Purpose

P-glycoprotein (Pgp) is an efflux transporter involved in transport of several compounds across the blood–brain barrier (BBB). Loss of Pgp function with increasing age may be involved in the development of age-related disorders, but this may differ between males and females. Pgp function can be quantified in vivo using ( R)-[ ¹¹C]verapamil and positron emission tomography. The purpose of this study was to assess global and regional effects of both age and gender on BBB Pgp function.

Procedures

Thirty-five healthy men and women in three different age groups were included. Sixty minutes dynamic ( R)-[ ¹¹C]verapamil scans with metabolite-corrected arterial plasma input curves were acquired. Grey matter time–activity curves were fitted to a validated constrained two-tissue compartment plasma input model, providing the volume of distribution ( V _T) of ( R)-[ ¹¹C]verapamil as outcome measure.

Results

Increased V _T of ( R)-[ ¹¹C]verapamil with aging was found in several large brain regions in men. Young and elderly women showed comparable V _T values. Young women had higher V _T compared with young men.

Conclusions

Decreased BBB Pgp is found with aging; however, effects of age on BBB Pgp function differ between men and women.