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

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

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

Topics: 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, UMCG Approved
Year: 2009
DOI identifier: 10.1016/j.neurobiolaging.2008.02.002
OAI identifier:
Provided by: NARCIS
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