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

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

Document Type: Research Article

DOI: https://doi.org/10.2174/156802610792928059

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

Publication date: 2010-12-01

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