Journal
NEUROBIOLOGY OF AGING
Volume 36, Issue 9, Pages 2475-2482Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.05.020
Keywords
P-glycoprotein; A beta; Blood-brain barrier; Aging; Alzheimer's disease
Categories
Funding
- PHS [MH/NS 31862]
- Saunders Family Fund at the Neurosurgery Foundation
- Rhode Island Hospital
- Warren Alpert Medical School, Brown University
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P-glycoprotein (P-gp), part of the blood-brain barrier, limits drug access to the brain and is the target for therapies designed to improve drug penetration. P-gp also extrudes brain amyloid-beta (A beta). Accumulation of A beta is a hallmark of Alzheimer's disease (AD). A beta accumulates in normal aging and in AD primarily due to decreased Ab clearance. This is a preliminary report on the relative protein and messenger RNA expression of P-gp in human brains, ages 20-100 years, including AD subjects. In these preliminary studies, cortical endothelial P-gp expression decreased in AD compared with controls (p < 0.001). Trends in P-gp expression in human aging are similar to aging rats. Microvessel P-gp messenger RNA remained unchanged with aging and AD. A beta plaques were found in 42.8% of normal subjects (54.5% of those older than 50 years). A qualitative analysis showed that P-gp expression is lower than the group mean in subjects older than 75 years but increased if younger. Decreased P-gp expression may be related to A beta plaques in aging and AD. Downregulating P-gp to allow pharmaceuticals into the central nervous system may increase A beta accumulation. (C) 2015 Elsevier Inc. All rights reserved.
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