Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice
Open accessAbstract
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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Tail biopsy samples were used to isolate DNA to confirm the genotype of the strain using previously established primers by PCR.
“Tail biopsy samples were used to isolate DNA to confirm the genotype of the strain using previously established primers by PCR93–95.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [94]
The Methods > Animals section identifies the APPswe/PS1ΔE9 mice used, but does not describe how their genotype was confirmed. Searches for tail-biopsy DNA, PCR genotyping, and primers found no passage describing the claimed procedure; the mention of marked tails in Methods > Fear conditioning concerns behavioral testing, not biopsy. (LLM, conf=0.72)
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- Authors
- LaClair, K. D., Manaye, K. F., Lee, D. L., Allard, J. S., Savonenko, A. V., Troncoso, J. C., & Wong, P. C.
- Affiliations
- Johns Hopkins University (US)
- Howard University (US)
- Corresponding author
- Troncoso, Juan C
- Wong, Philip C
- Venue
- Molecular Neurodegeneration
- Published
- 2013-06-13
- Volume
- 8
- Issue
- 1
- Pages
- 18-18
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC3693923
- OpenAlex
- W2474343990
- Cited by
- 83
- References
- 25
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 5 · 2016: 14 · 2015: 6 · 2014: 20 · 2013: 3
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-08-08)
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Johns Hopkins University
- Georgetown University
- Brain Science Institute, Johns Hopkins University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- bexarotene, apolipoprotein E, retinoid X receptor, ABCA1, amyloid-beta clearance, amyloid plaques, cognitive impairment, Alzheimer's disease, nuclear receptor agonists, amyloidosis
- MeSH terms
- Bexarotene, Alzheimer Disease, Animals, Apolipoproteins E, Behavior, Animal, Disease Models, Animal, Female, Male, Memory, Mice, Mutant Strains, Tetrahydronaphthalenes, Blotting, Western, Anticarcinogenic Agents, ATP-Binding Cassette Transporters, Mice, Plaque, Amyloid, ATP Binding Cassette Transporter 1
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