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. 2009 Sep;65(9):941-6.
doi: 10.1007/s00228-009-0709-5. Epub 2009 Aug 5.

Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET

Martin Bauer  1 , Rudolf Karch, Friederike Neumann, Aiman Abrahim, Claudia C Wagner, Kurt Kletter, Markus Müller, Markus Zeitlinger, Oliver Langer
Affiliations

Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET

Martin Bauer et al. Eur J Clin Pharmacol. 2009 Sep.

Abstract

Purpose: The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier.

Methods: Seven young (mean age: 27 +/- 4 years) and six elderly (mean age: 69 +/- 9 years) healthy volunteers underwent dynamic (R)-[(11)C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC).

Results: SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC.

Conclusions: Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age.

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Figures

Fig. 1
Fig. 1
Statistical parametric map for the comparison of VPM DVs (after PVC) between elderly and younger subjects. Yellow colour indicates regions with p<0.005. The “glass brain” visualises DV increases in cerebellum, frontal and temporal lobe. Merged with a normalised MRI the major increase can be located in cerebellum.
Fig. 2
Fig. 2
Correlation of VPM DVs in different brain ROIs (after PVC) with age in 7 young and 6 elderly subjects (male subjects: closed symbols; female subjects: open symbols). Shown are the linear correlation fits. Refer to table 1 for individual Pearson correlation coefficients (r).
Fig. 3
Fig. 3
Correlation of the influx rate constant K1 (left graph) and the efflux rate constant k2 (right graph) of VPM in different brain regions with age in 7 young and 6 elderly subjects (male subjects: closed symbols; female subjects: open symbols). Shown are the linear correlation fits. The negative correlation of k2 with age points to decreased transporter-mediated efflux at the BBB in age.
See this image and copyright information in PMC

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