Open Access Highly Accessed Research

Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent

Crissey L Pascale1, Miles C Miller1, Catherine Chiu1, Matthew Boylan1, Ilias N Caralopoulos1, Liliana Gonzalez2, Conrad E Johanson1 and Gerald D Silverberg1*

Author Affiliations

1 Warren Alpert Medical School Brown University, RI Hospital Department of Neurosurgery 593 Eddy St. Providence, RI 02903 USA

2 University of Rhode Island Department of Computer Science and Statistics Kingston, RI 02881 USA

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Fluids and Barriers of the CNS 2011, 8:21  doi:10.1186/2045-8118-8-21

Published: 8 July 2011

Abstract

Background

Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is an accumulation of amyloid-beta peptides (Aβ) in both the AD brain and the normal aging brain. Clearance of Aβ from the brain occurs via active transport at the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). With increasing age, the expression of the Aβ efflux transporters is decreased and the Aβ influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Aβ transporters at the choroid plexus (CP) epithelium as a function of aging was the subject of this study.

Methods

This project investigated the changes in expression of the Aβ transporters, the low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (P-gp), LRP-2 (megalin) and the receptor for advanced glycation end-products (RAGE) at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC) to measure transporter protein in isolated rat CP.

Results

There was an increase in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Aβ42 concentration in the CP, as measured by quantitative IHC, was associated with these Aβ transporter alterations.

Conclusions

Age-dependent alterations in the CP Aβ transporters are associated with a decrease in Aβ42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Aβ clearance in aging.

Keywords:
aging; amyloid-beta; transport; choroid plexus; blood-CSF-barrier; LRP-1; LRP -2; P-gp; RAGE