Blood-brain barrier P-glycoprotein function decreases in specific brain regions with aging: A possible role in progressive neurodegeneration

Anna L. Bartels*, Rudie Kortekaas, Joost Bart, Antoon T. M. Willemsen, Onno L. de Klerk, Jeroen J. de Vries, Joost C. H. van Oostrom, Klaus L. Leenders

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

116 Citations (Scopus)

Abstract

Cerebrovascular P-glycoprotein (P-gp) acts at the blood-brain barrier (BBB) as an active cell membrane efflux pump for several endogenous and exogenous compounds. Age-associated decline in P-gp function could facilitate the accumulation of toxic substances in the brain, thus increasing the risk of neurodegenerative pathology with aging. We hypothesised a regionally reduced BBB P-gp function in older healthy subjects.

We studied cerebrovascular P-gp function using [(11)C]-verapamil positron emission tomography (PET) in seventeen healthy volunteers with age 18-86. Logan analysis was used to calculate the distribution volume (DV) of [(11)C]-verapamil in the brain. Statistical Parametric Mapping was used to study specific regional differences between the older compared with the younger adults.

Older subjects showed significantly decreased P-gp function in internal capsule and corona radiata white matter and in orbitofrontal regions.

Decreased BBB P-gp function in those regions could thus explain part of the vulnerability of the aging brain to white matter degeneration. Moreover, decreased BBB P-gp function with aging could be a mechanism by which age acts as the main risk factor for the development of neurodegenerative disease. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1818-1824
Number of pages7
JournalNeurobiology of Aging
Volume30
Issue number11
DOIs
Publication statusPublished - Nov-2009

Keywords

  • Aging
  • P-glycoprotein
  • PET
  • [(11)C]-verapamil
  • Blood-brain barrier
  • Neurodegeneration
  • Alzheimer
  • Parkinson
  • White matter
  • POSITRON-EMISSION-TOMOGRAPHY
  • MULTIDRUG-RESISTANCE GENE
  • PARKINSONS-DISEASE
  • IN-VIVO
  • AMYLOID-BETA
  • ALZHEIMERS-DISEASE
  • ABC TRANSPORTERS
  • POTENTIAL ROLE
  • MOUSE-BRAIN
  • MDR1 GENE

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