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11C-verapamil to Assess P-gp Function in Human Brain During Aging,Depression and Neurodegenerative Disease

[ Vol. 10 , Issue. 17 ]

Author(s):

A. L. Bartels, O. L. de Klerk, R. Kortekaas, J. J. de Vries and K. L. Leenders   Pages 1775 - 1784 ( 10 )

Abstract:


P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a wide range of substrates from the brain. This is important for maintaining loco-regional homeostasis and for protecting the brain against blood-borne toxic substances. Altered P-gp function seems to be involved in the pathophysiology of neurodegenerative disease and various neurological and psychiatric disorders. Positron emission tomography (PET) with the radiotracer 11C-verapamil (VPM-PET) is a validated technique allowing measurement of P-gp function at the human BBB. In this review, we highlight changes of P-gp function, as measured with VPM-PET, in aging and in the pathogenesis and progression of neurodegenerative disease, as well as their role in depressive disorders.

Keywords:

P-glycoprotein, Blood-Brain Barrier, Ageing, Depression, Parkinson's Disease, Alzheimer's Disease, Positron Emission Tomography (PET), Verapamil, C-verapamil, P-glycoprotein (P-gp), Blood-brain barrier (BBB), (MRP), Central nervous system (CNS), Amyotrophic lateral sclerosis, Single-photon emission computed tomography, Tariquidar, P-gp expression, CD4+ and CD8+ T Cells, Statistical parametric mapping (SPM), Neurodegenerative disease, β-amyloid, ß-amyloid precursor protein (APP), ß-site APP cleaving enzyme (BACE), Lipoprotein receptor related protein 1 (LRP1), Cerebral amyloid angiopathy (CAA), P-gp inhibitor, Rifampicin, GSK188909, α-synuclein oligomers, C3435T TT polymorphism, Progressive supranuclear palsy (PSP), Multisystem atrophy (MSA), Pergolide, pramipexol, budipine, Huntington disease (HD), Creutzfeldt-Jakob Disease (CJD), Amyotrophic lateral sclerosis (ALS), Major depressive disorder (MDD)

Affiliation:

Dept. of Neurology, University Medical Center Groningen, The Netherlands.



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