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

Department of Neurology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Neurobiology of aging (Impact Factor: 5.94). 04/2008; 30(11):1818-24. DOI: 10.1016/j.neurobiolaging.2008.02.002
Source: PubMed

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.

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