Journal of Molecular Neuroscience

, Volume 49, Issue 2, pp 270–276

Stimulation of the Retinoid X Receptor Facilitates Beta-Amyloid Clearance Across the Blood–Brain Barrier

  • Corbin Bachmeier
  • David Beaulieu-Abdelahad
  • Fiona Crawford
  • Michael Mullan
  • Daniel Paris
Article

Abstract

Alzheimer’s disease (AD) is a neurodegenerative process characterized, in part, by the accumulation of beta-amyloid proteins (Aβ) in the brain. Evidence now suggests that the excessive Aβ accumulation is the result of impaired clearance from the brain. Recent studies have indicated that retinoid X receptor (RXR) activation stimulates the metabolic clearance of Aβ and rapidly reverses Aβ-induced behavioral deficits, doing so in an apoE-dependent manner. Previously, we reported that soluble apoE (i.e., not bound to Aβ) facilitated Aβ transit across the blood–brain barrier (BBB). As Aβ clearance from the brain involves both metabolic and BBB-mediated processes, the current studies investigated the impact of RXR stimulation on Aβ clearance across the BBB. Treatment with RXR agonists increased Aβ clearance across the BBB both in vitro and in vivo. Moreover, this processes appeared to involve apoE as RXR agonism did not stimulate Aβ BBB clearance when apoE was absent. Thus, RXR activation could mitigate Aβ brain burden by promoting both the metabolic and BBB clearance of Aβ, offering a novel approach to the treatment of AD.

Keywords

Alzheimer’s disease Amyloid Retinoid X receptor Apolipoprotein E Blood–brain barrier 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Corbin Bachmeier
    • 1
  • David Beaulieu-Abdelahad
    • 1
  • Fiona Crawford
    • 1
  • Michael Mullan
    • 1
  • Daniel Paris
    • 1
  1. 1.The Roskamp InstituteSarasotaUSA

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