ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Reversal of apoE4-driven brain pathology and behavioral deficits by bexarotene.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Pooled it
- ApoE4 as a Therapeutic Target in Epilepsy: From Pathogenic Mechanisms to Precision Medicine.CNS neuroscience & therapeutics · 2026Review
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Brain Amyloid Deposition Is Negatively Associated with Cardiac Amyloid Retention in Apo E4 Carriers: A Pilot Study.Molecular imaging and biology · 2026Article
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- Brain Single-Cell Transcriptional Responses to Bexarotene-Activated RXR in an Alzheimer's Disease Model.International journal of molecular sciences · 2026Article
- Article
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Apolipoprotein E in Alzheimer's disease: molecular insights and therapeutic opportunities.Molecular neurodegeneration · 2025Review
- Carotenoid Supplementation for Alleviating the Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Multifaceted roles of APOE in Alzheimer disease.Nature reviews. Neurology · 2024Review
- Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist.Neuron · 2024Article
- The Role of Impaired Receptor Trafficking in Mediating the Pathological Effects of APOE4 in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Modeling sporadic Alzheimer's disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors.Frontiers in aging neuroscience · 2024Article
- A novel apoE-mimetic increases brain apoE levels, reduces Aβ pathology and improves memory when treated before onset of pathology in male mice that express APOE3.Alzheimer's research & therapy · 2023Article
- Apolipoprotein E in lipid metabolism and neurodegenerative disease.Trends in endocrinology and metabolism: TEM · 2023Review
- Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise.The FEBS journal · 2023Review
- ApoE3 vs. ApoE4 Astrocytes: A Detailed Analysis Provides New Insights into Differences in Cholesterol Homeostasis.Antioxidants (Basel, Switzerland) · 2022Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is less lipidated than its corresponding AD-benign form, apoE3, and it has been suggested that the pathological effects of apoE4 are mediated by lipid-related mechanisms. ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1, respectively) are the most important apoE-lipidating proteins. The expression of these proteins, as well as that of apoE, is controlled by the transcription regulation retinoid X receptor (RXR)-liver X receptor (LXR) system. In the present study, we investigated the effects of the RXR agonist bexarotene on mRNA and protein levels of apoE, ABCA1, and ABCG1 in young, naive apoE3- and apoE4-targeted replacement mice and assessed the extent to which this reverses the apoE4-driven pathological phenotype. This investigation reveled that bexarotene increases the mRNA and protein levels of ABCA1 and ABCG1 in hippocampal neurons, but has no effect on the corresponding levels of apoE. These findings were associated with reversal of the lipidation deficiency of apoE4 and of the cognitive impairments of apoE4 mice in several tests. Furthermore, bexarotene reversed the apoE4-driven accumulation of Aβ42 and hyperphosphorylated tau in hippocampal neurons, as well as the apoE4-induced reduction in the levels of the presynaptic marker vesicular glutamatergic transporter 1 (VGluT1). In conclusion, the results show that treatment of apoE4 mice with the RXR agonist bexarotene reverses the apoE4-induced cognitive and neuronal impairments in vivo and suggest that this is due to reversal of the lipidation deficiency of apoE4. This puts forward the possibility that RXR activation and increased levels of ABCA1 and ABCG1 could be useful in the treatment of human apoE4 carriers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.