Skip to main content


We're creating a new version of this page. See preview

  • Poster presentation
  • Open Access

Bexarotene treatment does not clear β-Amyloid in an AD mouse model and Beagle dogs

  • 1, 2,
  • 3,
  • 1, 2,
  • 1,
  • 4,
  • 4,
  • 4,
  • 4,
  • 4,
  • 4,
  • 3 and
  • 1, 2
Molecular Neurodegeneration20138 (Suppl 1) :P40

  • Published:


  • Genetic Risk Factor
  • Aging Society
  • Behavioral Alteration
  • Clearance Mechanism
  • Bexarotene


In our aging society Alzheimer’s Disease (AD) is becoming more and more prevalent while effective symptomatic therapeutics remain limited and no cure is available. ApoE4 is the most important genetic risk factor for AD. Previous results by Cramer et al. [1] showed that Bexarotene treatment reduced Aβ in the brain of wild type and AD model mice via an apoE-mediated clearance mechanism. Bexarotene, an RXR agonist, is an FDA approved drug for cutaneous T cell lymphoma and hence a preferred candidate for clinical testing. In this study we attempted to replicate the data by Cramer et al. [1].


We used captisol® (Cydex Pharmaceuticals), and HP-b-CD/ Tween to dissolve Bexarotene for administration in mice and dogs respectively. For acute experiments we administered a single 100 mg/kg/p.o. dose of Bexarotene (Ontario Chemical, Inc., Canada) to wild type male Swiss CD1 mice and measured endogenous levels of soluble Aβx-37, Aβx-38, Aβx-40 and Aβx-42 in brain at different time points. In Beagle dogs we administered 25 and 100 mg/kg/p.o. Bexarotene and measured Aβx-37, Aβx-38, Aβx-40 and Aβx-42 levels in CSF. For chronic experiments we administered 100 mg/kg/day/p.o. Bexarotene for 19 days to 10-months-old male hAPP/PS1 mice.


In contrast to the published data, we found that acute and chronic treatment with Bexarotene had no significant effects on Aβ levels in the brain of wild type and AD model mice and in Beagle dogs, despite high penetration of the drug into the brain. Although behavioral alterations were observed in AD model mice, adverse effects of the treatment confounded these observations.


Drug formulation and pharmacokinetics might explain our contradictory observations with Cramer et al. [1] at least partly. These issues need to be resolved before Bexarotene can be tested in AD.

Authors’ Affiliations

VIB Center for the Biology of Disease, Leuven, Belgium
KU Leuven and Universitaire Ziekenhuizen, Center for Human Genetics and Institute of Neuroscience & Disease (LIND), Leuven, Belgium
Laboratory of Biological Psychology and Leuven Institute of Neuroscience & Disease (LIND), University of Leuven, Leuven, Belgium
Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium


  1. Cramer PE, Cirrito JR: ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science. 2012, 335: 1503-1506. 10.1126/science.1217697.PubMed CentralView ArticlePubMedGoogle Scholar


© Tesseur et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.