The Continuing Failure of Bexarotene in Alzheimer's Disease Mice

Journal of Alzheimer's Disease : JAD
Claudia BalducciGianluigi Forloni

Abstract

Alzheimer's disease (AD) is the most common form of dementia characterized by synaptic dysfunction, memory loss, neuroinflammation, and neuronal cell death. Amyloid-β (Aβ), recognized as the main culprit of AD, aggregates and accumulates in the extracellular compartment as neuritic plaques, after deregulation of its production or clearance. Apolipoprotein E (ApoE) plays a major role in Aβ clearance and its expression is transcriptionally regulated by the liver X receptor and retinoid X receptors (RXRs) system. Bexarotene (BEXA), an RXR agonist that increases ApoE expression and microglia phagocytosis has been proposed as a promising therapy for AD, resolving both the amyloid pathology and memory loss. Despite the first compelling report, however, multiple failures have been documented, raising concern about whether BEXA could in fact become a novel disease-modifying strategy for AD. To help clarify this, we investigated the effect of BEXA in vivo at multiple levels in TASTPM transgenic mice. Seven-day oral administration of BEXA to these mice did not achieve any significant memory improvement, plaque reduction, or enhancement of microglial cell activation. No differences were found when specifically investigating the microglial...Continue Reading

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Citations

Jan 30, 2016·Alzheimer's Research & Therapy·Jeffrey L CummingsJames Bena
Jan 5, 2016·Journal of Neurology·Javier RianchoMiguel Lafarga
Oct 8, 2015·Journal of Alzheimer's Disease : JAD·Nathalie PierrotAdrian Ivanoiu
Nov 12, 2016·Journal of Alzheimer's Disease : JAD·Fiammetta MonacelliAlessio Nencioni
Apr 14, 2016·PloS One·Joseph RosenthalDavid Isaacson
Jun 24, 2017·Antioxidants & Redox Signaling·Maria Valeria CataniMauro Maccarrone
Mar 30, 2019·British Journal of Pharmacology·Nicholas F FitzIliya Lefterov
Apr 1, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Gianluigi ForloniClaudia Balducci
Nov 20, 2016·Journal of Molecular Neuroscience : MN·Niyaz Mohammadzadeh HonarvarGerald Muench
May 30, 2016·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Linda J Van EldikKelly Bales
Nov 14, 2020·Acta Neuropathologica Communications·Angie C A ChiangCobi J Heijnen
Nov 6, 2020·Molecular Neurodegeneration·Zonghua LiGuojun Bu

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