| First Author | Cramer PE | Year | 2012 |
| Journal | Science | Volume | 335 |
| Issue | 6075 | Pages | 1503-6 |
| PubMed ID | 22323736 | Mgi Jnum | J:181688 |
| Mgi Id | MGI:5313740 | Doi | 10.1126/science.1217697 |
| Citation | Cramer PE, et al. (2012) ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335(6075):1503-6 |
| abstractText | Alzheimer's disease (AD) is associated with impaired clearance of beta-amyloid (Abeta) 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 agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Abeta within hours in an apoE-dependent manner. Abeta plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Abeta clearance mechanisms, resulting in the rapid reversal of a broad range of Abeta-induced deficits. |
