P-glycoprotein function at the blood-brain barrier: effects of age and gender

Mol Imaging Biol. 2012 Dec;14(6):771-6. doi: 10.1007/s11307-012-0556-0.

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)-[(11)C]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)-[(11)C]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)-[(11)C]verapamil as outcome measure.

Results: Increased V (T) of (R)-[(11)C]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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Aged
  • Aging / metabolism*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Regression Analysis
  • Sex Characteristics*
  • Verapamil / administration & dosage
  • Verapamil / pharmacology
  • Young Adult

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Verapamil