期刊
JOURNAL OF NUCLEAR MEDICINE
卷 55, 期 7, 页码 1106-1111出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.113.130161
关键词
Alzheimer's disease; blood-brain barrier; P-glycoprotein activity; PET imaging; relative extraction ratio
资金
- AHAF [A2007-086]
- National Institute of Aging [031485]
- NCRR [TL1 RR 025016]
- ITHS TL1 Multidisciplinary Predoctoral Clinical Research Training Program [PHS2271]
Studies in animals and postmortem human brain tissue support a role for P-glycoprotein in clearance of cerebral beta-amyloid across the blood-brain barrier (BBB). We tested the hypothesis that BBB P-glycoprotein activity is diminished in Alzheimer disease (AD) by accounting for an AD-related reduction in regional cerebral blood flow (rCBF). Methods: We compared P-glycoprotein activity in mild-AD patients (n = 9) and cognitively normal, age-matched controls (n = 9) using PET with a labeled P-glycoprotein substrate, C-11-verapamil, and O-15-water to measure rCBF. BBB P-glycoprotein activity was expressed as the C-11-verapamil radioactivity extraction ratio (C-11-verapamil brain distributional clearance, K-1/rCBF). Results: Compared with controls, BBB P-glycoprotein activity was significantly lower in the parietotemporal, frontal, and posterior cingulate cortices and hippocampus of mild AD subjects. Conclusion: BBB P-glycoprotein activity in brain regions affected by AD is reduced and is independent of rCBF. This study improves on prior work by eliminating the confounding effect that reduced rCBF has on assessment of BBB P-glycoprotein activity and suggests that impaired P-glycoprotein activity may contribute to cerebral beta-amyloid accumulation in AD. P-glycoprotein induction or activation to increase cerebral beta-amyloid clearance could constitute a novel preventive or therapeutic strategy for AD.
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