ApoE-Directed Therapeutics Rapidly Clear beta-Amyloid and Reverse Deficits in AD Mouse Models

作者：Cramer, Paige E.; Cirrito, John R.; Wesson, Daniel W.; Lee, C. Y. Daniel; Karlo, J. Colleen; Zinn, Adriana E.; Casali, Brad T.; Restivo, Jessica L.; Goebel, Whitney D.; James, Michael J.; Brunden, Kurt R.; Wilson, Donald A.; Landreth, Gary E.^*

来源：Science, 2012, 335(6075): 1503-1506.

DOI：10.1126/science.1217697

• ALZHEIMERS-DISEASE
• COMMON VARIANTS
• DYSFUNCTION
• BURDEN
• MICE
• METABOLISM
• RECEPTORS
• PATHOLOGY
• MEMORY
• CD2AP

Alzheimer's disease (AD) is associated with impaired clearance of beta-amyloid (A beta) 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 A beta within hours in an apoE-dependent manner. A beta 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 A beta clearance mechanisms, resulting in the rapid reversal of a broad range of A beta-induced deficits.

• 出版日期2012-3-23