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Open Access 01-12-2013 | Short report

Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice

Authors: Katherine D LaClair, Kebreten F Manaye, Dexter L Lee, Joanne S Allard, Alena V Savonenko, Juan C Troncoso, Philip C Wong

Published in: Molecular Neurodegeneration | Issue 1/2013

Abstract

Background

Though the precise cause(s) of Alzheimer’s disease (AD) remain unknown, there is strong evidence that decreased clearance of β-amyloid (Aβ) from the brain can contribute to the disease. Therapeutic strategies to promote natural Aβ clearance mechanisms, such as the protein apolipoprotein-E (APOE), hold promise for the treatment of AD. The amount of APOE in the brain is regulated by nuclear receptors including retinoid X receptors (RXRs). Drugs that activate RXRs, including bexarotene, can increase APOE and ABCA1 production, and have been shown to decrease the Aβ burden and improve cognition in mouse models of Aβ amyloidosis. Although recent bexarotene studies failed to replicate the rapid clearance of Aβ from brains, behavioral and cognitive effects of this compound remain controversial.

Findings

In efforts to clarify these behavioral findings, mutant APP/PS1 mice were acutely dosed with bexarotene. While ABCA1 was upregulated in mutant APP/PS1 mice treated with bexarotene, this drug failed to attenuate Aβ plaques or cognitive deficits in these mice.

Conclusions

We recommend rigorous preclinical study to evaluate the mechanism and utility of such a compound for AD therapy.

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Title: Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice
Authors: Katherine D LaClair
Kebreten F Manaye
Dexter L Lee
Joanne S Allard
Alena V Savonenko
Juan C Troncoso
Philip C Wong
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2013
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-8-18

At a glance: The STEP trials

Springer Medicine

Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice

Abstract

Background

Findings

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Findings

Conclusions

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