title: P-glycoprotein function at the blood-brain barrier: effects of age and gender.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Nuclear Medicine & PET Research, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. d.vanassema@vumc.nl
authors.forename: Daniëlle M E
authors.initials: DM
authors.lastname: van Assema
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012727:Sex Characteristics; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014700:Verapamil