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Amyloid-β pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo.

Author: Ben AissaManel, CollinsNicole C, KosterKevin P, LaDuMary Jo, LeeSue H, LuoJia, TaiLeon M, ThatcherGregory R J, WangYue-Ting

Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

Bexarotene, a retinoid X receptor (RXR) agonist, has shown promise in reducing amyloid-β (Aβ) in Alzheimer’s disease (AD) transgenic mice. However, the use of RXR agonists is limited by concerns about human apolipoprotein E4 (APOE4), the greatest genetic risk factor for AD. This study investigated the effects of bexarotene in mice overexpressing human Aβ42 and APOE4. Results show that bexarotene increased ABCA1, apoE4 lipoprotein association/lipidation, and apoE4/Aβ complex, decreased soluble Aβ, and increased PSD95. However, bexarotene also increased soluble Aβ levels in some mice, suggesting potential systemic side effects.
Paper Details　
Original Abstract of the Article :
Previous data demonstrate that bexarotene (Bex), retinoid X receptor (RXR) agonist, reduces soluble and insoluble amyloid-β (Aβ) in Alzheimer disease (AD)-transgenic mice either by increasing the levels of mouse apolipoprotein E (apoE) or increasing ABCA1/ABCG1-induced apoE lipoprotein association/l...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215234/

データ提供：米国国立医学図書館（NLM）

Investigating the Impact of APOE Genotype on Retinoid X Receptor Agonist Activity in Alzheimer's Disease

This research examines the role of APOE genotype, a major genetic risk factor for Alzheimer's disease (AD), in modulating the activity of retinoid X receptor (RXR) agonists in a mouse model of AD. The study uses transgenic mice overexpressing human Aβ42 and human APOE to investigate the effects of RXR agonists on soluble and insoluble amyloid-β (Aβ) levels. The findings suggest that RXR agonists may be beneficial in reducing Aβ levels in mice carrying the APOE3 allele, but may have less efficacy in mice with the APOE4 allele. The authors conclude that RXR agonists may hold therapeutic potential for AD, but further research is needed to optimize their use in patients with different APOE genotypes.

Understanding the Potential Role of APOE Genotype in Alzheimer's Disease Treatment

This research highlights the complex interplay between genetic factors and therapeutic responses in AD. The study's findings suggest that APOE genotype may significantly impact the efficacy of RXR agonists in reducing Aβ levels. This underscores the need for personalized therapeutic approaches that consider individual genetic profiles.

The Complexities of Alzheimer's Disease Research

This research underscores the challenges and complexities of developing effective therapies for AD. The study's findings highlight the need for a deeper understanding of the genetic and molecular mechanisms underlying the disease to develop personalized treatments.

Dr. Camel's Conclusion

This research reminds me of the intricate puzzle of AD, where each piece, like a grain of sand in the desert, plays a crucial role. Understanding the interplay of genes, environment, and therapeutic interventions is essential to finding effective solutions for this challenging disease. This study encourages us to continue our quest for knowledge and to explore new avenues of research to combat the devastating effects of AD.
Date :
  1. Date Completed 2014-12-31
  2. Date Revised 2021-10-21
Further Info :

Pubmed ID

25217640

DOI: Digital Object Identifier

PMC4215234

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Languages

English

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