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 (VT) of (R)-[11C]verapamil as outcome measure. Results: Increased VT of (R)-[11C]verapamil with aging was found in several large brain regions in men. Young and elderly women showed comparable VT values. Young women had higher VT 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. © World Molecular Imaging Society, 2011.