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

A.      L. Bartels; O.      L. de Klerk; R.      Kortekaas; J.      J. de Vries; K.      L. Leenders

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)