Bexarotene treatment does not clear β-Amyloid in an AD mouse model and Beagle dogs

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ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.

Alzheimer's disease (AD) is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR ...

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Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models".

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 si...

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Comment on “ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models”

Cramer et al. (Reports, 23 March 2012, p. 1503; published online 9 February 2012) reported that bexarotene rapidly reduces b-amyloid (Ab) levels and plaque burden in two mouse models of Ab deposition in Alzheimer’s disease (AD). We now report that, although bexarotene reduces soluble Ab40 levels in one of the mouse models, the drug has no impact on plaque burden in three strains that exhibit Ab...

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Comment on “ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models”

ApoE4 is the most important genetic risk factor for Alzheimer’s disease (AD) (1), and we therefore read with great interest the paper by Cramer et al. (2) demonstrating spectacular results of bexarotene on b-amyloid (Ab) accumulation in the brain of mouse models for AD. Bexarotene is a retinoid X receptor (RXR) agonist and approved by the U.S. Food and Drug Administration (FDA) for treatment of...

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Bexarotene reduces network excitability in models of Alzheimer's disease and epilepsy.

The nuclear retinoid X receptor agonist, bexarotene, has been implicated in recovery of cognitive function in mouse models of Alzheimer's disease (AD). Since AD genetic mouse models also show abnormal neural hyperexcitability, which may play a destructive role in memory storage and retrieval, we studied whether bexarotene exerted dynamic network effects on electroencephalography cortical spike ...

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ژورنال

عنوان ژورنال: Molecular Neurodegeneration

سال: 2013

ISSN: 1750-1326

DOI: 10.1186/1750-1326-8-s1-p40