دورية أكاديمية
Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients
| العنوان: | Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients |
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| المؤلفون: | Assema, D.M.E. (Daniëlle) van, Lubberink, M. (Mark), Rizzu, P. (Patrizia), Swieten, J.C. (John) van, Schuit, R.C. (Robert), Eriksson, J. (Joel), Scheltens, P. (Philip), Koepp, M. (Matthias), Lammertsma, A.A. (Adriaan), Berckel, B.N.M. (Bart ) van |
| المصدر: | EJNMMI Research vol. 2 no. 1, pp. 1-6 |
| سنة النشر: | 2012 |
| المجموعة: | RePub - Publications from Erasmus University, Rotterdam |
| مصطلحات موضوعية: | ABCB1, (R)-[11C]verapamil, Blood-brain barrier, MDR1, P-glycoprotein, PET, Polymorphisms |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | info:eu-repo/grantAgreement/EC/FP7/201380; http://repub.eur.nl/pub/39741Test; urn:hdl:1765/39741 |
| DOI: | 10.1186/2191-219X-2-57 |
| الإتاحة: | https://doi.org/10.1186/2191-219X-2-57Test http://repub.eur.nl/pub/39741Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1D619BD6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/2191-219X-2-57 |
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