Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”
Open accessAbstract
Cramer et al . (Reports, 23 March 2012, p. 1503; published online 9 February 2012) demonstrated in a mouse model for Alzheimer’s disease (AD) that treatment of APP/PS1ΔE9 mice with bexarotene decreased Aβ pathology and ameliorated memory deficits. We confirm the reversal of memory deficits in APP/PS1ΔE9 mice expressing human APOE3 or APOE4 to the levels of their nontransgenic controls and the significant decrease of interstitial fluid Aβ, but not the effects on amyloid deposition.
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Treatment with LXR/RXR agonists increases levels of ABCA1 and APOE and decreases amyloid deposition in APP overexpressing cells and mice.
“Several studies demonstrated that treatment of LXR/RXR agonists increase the levels of ABCA1 and APOE and decrease amyloid deposition in APP overexpressing cells and mice [73-77].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [75]
The paper reports increased ABCA1 and APOE protein levels after bexarotene treatment, but its findings contradict the attributed decrease in amyloid deposition. In the section labeled Abstract, it reports no significant difference in plaques between treated and control APP/E3 or APP/E4 mice, while distinguishing that result from a decrease in interstitial-fluid Aβ. It does not report a cell experiment. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe effects of bexarotene have been variable in most follow-up studies.
“the effects of bexarotene have been variable in most follow-up studies (13, 14, 15, 16)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [13]
In the Abstract, this follow-up study reports mixed effects: bexarotene improved memory and reduced interstitial-fluid Aβ, but did not reduce amyloid deposition. It supports variability in this study’s results, but does not establish what happened in most follow-up studies. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe therapeutic effects of RXR agonists, especially bexarotene, varied widely in follow-up studies.
“the therapeutic effects of RXR agonists, especially bexarotene, varied widely in follow-up studies (13, 14, 15, 16)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [13]
Subsequent studies reproduced the ability of bexarotene to reverse AD-related behavioral deficits.
“Subsequent studies reproduced the ability of bexarotene to reverse AD-related behavioral deficits9194647.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [19]
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- Authors
- Fitz, N. F., Cronican, A. A., Lefterov, I., & Koldamova, R.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Lefterov, Iliya
- Koldamova, Radosveta
- Venue
- Science
- Published
- 2013-05-24
- Volume
- 340
- Issue
- 6135
- Pages
- 924-924
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4086452
- OpenAlex
- W3145943915
- Cited by
- 151
- References
- 14
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 10 · 2018: 9 · 2017: 13 · 2016: 22 · 2015: 27 · 2014: 28 · 2013: 13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG037481, F32AG034031, R01AG037919)
- National Institute of Environmental Health Sciences (R21ES021243)
- 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
- Alzheimer's disease, amyloid-beta, APOE ε4, APOE3, bexarotene, memory impairment, amyloid deposition
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Male, Tetrahydronaphthalenes, Amyloid beta-Peptides
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