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

The goal of this study was to further assess the therapeutic potential of bexarotene  and  replicate the findings results of Cramer et al, 2013. Since bexarotene is reportedly not soluble in water investigators used a different formulation (DMSO+ polyethylene glycol) of bexarotene than that of Cramer et al (water). Results show that at the end of the dosing regimen  beta amyloid load  and soluble beta amyloid peptide levels were not significantly reduced compared to vehicle control. Although no significant effects were detected on the two primary outcome measures data indicated that the drug engaged the target. These data suggest that the reported effect of bexarotene in clearing Abeta deposits is not easily reproducible.The authors urge that further validation studies be conducted before considering human AD bexarotene clinical trials. They further state that the potential “off-label” use of this drug for AD treatment needs to be tempered by compelling and reproducible preclinical data.