RT Journal Article
SR Electronic
T1 Activity of P-Glycoprotein, a β-Amyloid Transporter at the Blood–Brain Barrier, Is Compromised in Patients with Mild Alzheimer Disease
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1106
OP 1111
DO 10.2967/jnumed.113.130161
VO 55
IS 7
A1 Anand K. Deo
A1 Soo Borson
A1 Jeanne M. Link
A1 Karen Domino
A1 Janet F. Eary
A1 Ban Ke
A1 Todd L. Richards
A1 David A. Mankoff
A1 Satoshi Minoshima
A1 Finbarr O’Sullivan
A1 Sara Eyal
A1 Peng Hsiao
A1 Ken Maravilla
A1 Jashvant D. Unadkat
YR 2014
UL http://jnm.snmjournals.org/content/55/7/1106.abstract
AB Studies in animals and postmortem human brain tissue support a role for P-glycoprotein in clearance of cerebral β-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, 11C-verapamil, and 15O-water to measure rCBF. BBB P-glycoprotein activity was expressed as the 11C-verapamil radioactivity extraction ratio (11C-verapamil brain distributional clearance, K1/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 β-amyloid accumulation in AD. P-glycoprotein induction or activation to increase cerebral β-amyloid clearance could constitute a novel preventive or therapeutic strategy for AD.