2012-12-01
Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients
Publication
Publication
Effect of polymorphisms in the ABCB1 gene
EJNMMI Research , Volume 2 - Issue 1 p. 1- 6
Background: P-glycoprotein is a blood-brain barrier efflux transporter involved in the clearance of amyloid-beta from the brain and, as such, might be involved in the pathogenesis of Alzheimer's disease. P-glycoprotein is encoded by the highly polymorphic ABCB1 gene. Single-nucleotide polymorphisms in the ABCB1 gene have been associated with altered P-glycoprotein expression and function. P-glycoprotein function at the blood-brain barrier can be quantified in vivo using the P-glycoprotein substrate tracer (R)-[11C]verapamil and positron emission tomography (PET). The purpose of this study was to assess the effects of C1236T, G2677T/A and C3435T single-nucleotide polymorphisms in ABCB1 on blood-brain barrier P-glycoprotein function in healthy subjects and patients with Alzheimer's disease. Methods: Thirty-two healthy subjects and seventeen patients with Alzheimer's disease underwent 60-min dynamic (R)-[11C]verapamil PET scans. The binding potential of (R)-[11C]verapamil was assessed using a previously validated constrained two-tissue plasma input compartment model and used as outcome measure. DNA was isolated from frozen blood samples and C1236T, G2677T/A and C3435T single-nucleotide polymorphisms were amplified by polymerase chain reaction. Results: In healthy controls, binding potential did not differ between subjects without and with one or more T present in C1236T, G2677T and C3435T. In contrast, patients with Alzheimer's disease with one or more T in C1236T, G2677T and C3435T had significantly higher binding potential values than patients without a T. In addition, there was a relationship between binding potential and T dose in C1236T and G2677T. Conclusions: In Alzheimer's disease patients, C1236T, G2677T/A and C3435T single-nucleotide polymorphisms may be related to changes in P-glycoprotein function at the blood-brain barrier. As such, genetic variations in ABCB1 might contribute to the progression of amyloid-beta deposition in the brain.
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| doi.org/10.1186/2191-219X-2-57, hdl.handle.net/1765/39741 | |
| EJNMMI Research | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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van Assema, D., Lubberink, M., Rizzu, P., van Swieten, J., Schuit, R., Eriksson, J., … van Berckel, B. (2012). Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients. EJNMMI Research, 2(1), 1–6. doi:10.1186/2191-219X-2-57 |
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