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

Katherine D. Laclair, Kebreten F. Manaye, Dexter L. Lee, Joanne S. Allard, Alena Savonenko, Juan C Troncoso, Philip Chun Wong

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number18
JournalMolecular Neurodegeneration
Volume8
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Apolipoproteins E
Retinoid X Receptors
Alzheimer Disease
Brain
Amyloidosis
Cytoplasmic and Nuclear Receptors
Amyloid
Pharmaceutical Preparations
Cognition
bexarotene
Therapeutics
Proteins

Keywords

  • Alzheimer's disease
  • APOE
  • Bexarotene
  • Cognition
  • Mouse model
  • RXR agonist

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

Cite this

Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice. / Laclair, Katherine D.; Manaye, Kebreten F.; Lee, Dexter L.; Allard, Joanne S.; Savonenko, Alena; Troncoso, Juan C; Wong, Philip Chun.

In: Molecular Neurodegeneration, Vol. 8, No. 1, 18, 2013.

Research output: Contribution to journalArticle

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