Name: Bexarotene
Synonyms: Targretin®
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline), Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Ligand Pharmaceuticals, Inc., ReXceptor Inc.
Approved for: Cutaneous T-cell Lymphoma in US


This retinoid drug is approved by the FDA and EMA to treat T cell lymphoma of the skin. It is an agonist of a nuclear transcription factor called retinoid X receptor, which forms heterodimers with peroxisome proliferator-activated receptor γ (PPARγ) or liver X receptors (LXRs) to aid in the formation of ApoE lipoprotein particles. In 2012, bexarotene was reported to rapidly increase brain ApoE concentration, reduce interstitial fluid Aβ levels and amyloid deposition, and reverse cognitive deficits in APP/PS1 mouse models (Feb 2012 news). Subsequent studies, using the same or different rodent models and outcome measures, replicated only portions of the original findings (May 2013 news; Laclair et al., 2013; O'Hare et al., 2016). Other preclinical studies have implicated bexarotene in ApoE lipidation, reported ApoE isoform-specific effects, or postulated that bexarotene dampens network hyperexcitability (May 2014 newsSep 2014 newsBomben et al., 2014).


In 2014, a Phase 2 biomarker proof-of-concept study at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas evaluated the effect of a one-month blinded course of 300 mg bexarotene per day, followed by another month of open-label treatment. The primary outcome was brain amyloid load in 20 patients with probable Alzheimer's disease. Results published in January 2016 indicated no reduction in overall or regional amyloid burden in the group as a whole. A prespecified subgroup analysis by ApoE genotype found no amyloid reduction in ApoE4 carriers, but in ApoE4 non-carriers it did find regional amyloid reductions. These correlated with elevated serum Aβ42. Bexarotene-treated patients had significantly elevated blood lipid levels, a risk factor for stroke and heart attack (Cummings et al., 2016).

Also in 2014, a Phase 1 proof-of-mechanism pilot study conducted by ReXceptor Inc. and C2N in Orlando, Florida, began. It measures generation and clearance of newly generated CSF Aβ and ApoE in response to a five-day course of 450 mg bexarotene per day. This study enrolled 12 young healthy adults who are homozygote ApoE3 carriers. It found that bexarotene poorly entered the central nervous system. The plasma to CSF ratio was 85:1, with bexarotene below the limit of quantitation in most CSF samples. CSF ApoE increased by one-quarter, but Abeta peptides did not change (Ghosal et al., 2016).

For all bexarotene Alzheimer trials, see  

Last Updated: 16 Aug 2019


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News Citations

  1. Upping Brain ApoE, Drug Treats Alzheimer's Mice
  2. Bexarotene Revisited: Improves Mouse Memory But No Effect on Plaques
  3. Has ApoE’s Time Come as a Therapeutic Target?
  4. Bexarotene’s Effects Vary by ApoE Genotype, Amyloid Pathology

Paper Citations

  1. . Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease. Alzheimers Res Ther. 2016 Jan 29;8:4. PubMed.
  2. . A randomized controlled study to evaluate the effect of bexarotene on amyloid-β and apolipoprotein E metabolism in healthy subjects. Alzheimers Dement (N Y). 2016 Jun;2(2):110-120. Epub 2016 Jun 17 PubMed.
  3. . Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice. Mol Neurodegener. 2013;8:18. PubMed.
  4. . Lack of support for bexarotene as a treatment for Alzheimer's disease. Neuropharmacology. 2016 Jan;100:124-30. Epub 2015 May 27 PubMed.
  5. . Bexarotene reduces network excitability in models of Alzheimer's disease and epilepsy. Neurobiol Aging. 2014 Sep;35(9):2091-5. Epub 2014 Apr 2 PubMed.

External Citations


Further Reading


  1. . Bexarotene Promotes Cholesterol Efflux and Restricts Apical-to-Basolateral Transport of Amyloid-β Peptides in an In Vitro Model of the Human Blood-Brain Barrier. J Alzheimers Dis. 2015;48(3):849-62. PubMed.
  2. . The emerging role of bexarotene in the treatment of Alzheimer's disease: current evidence. Neuropsychiatr Dis Treat. 2015;11:311-5. Epub 2015 Feb 5 PubMed.
  3. . Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab. 2007 Jul;92(7):2496-9. Epub 2007 Apr 17 PubMed.
  4. . Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001 May;137(5):581-93. PubMed.
  5. . Bexarotene for the treatment of cognitive decline in an individual with Alzheimer’s dementia. Alzheimers Dement. 2013 Jul;9(4 Suppl):P301.
  6. . Bexarotene blocks calcium-permeable ion channels formed by neurotoxic Alzheimer's β-amyloid peptides. ACS Chem Neurosci. 2014 Mar 19;5(3):216-24. Epub 2014 Jan 12 PubMed.