Science. 2012 Mar 23;335(6075):1503-6. doi: 10.1126/science.1217697. Epub 2012 Feb 9.

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

Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE.

Source

Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Abstract

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 agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ 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 Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits.

Comment in

Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models". [Science. 2013]
Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models".Price AR, Xu G, Siemienski ZB, Smithson LA, Borchelt DR, Golde TE, Felsenstein KM. Science. 2013 May 24; 340(6135):924-d.
Response to comments on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models". [Science. 2013]
Response to comments on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models".Landreth GE, Cramer PE, Lakner MM, Cirrito JR, Wesson DW, Brunden KR, Wilson DA. Science. 2013 May 24; 340(6135):924-g.
Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models". [Science. 2013]
Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models".Veeraraghavalu K, Zhang C, Miller S, Hefendehl JK, Rajapaksha TW, Ulrich J, Jucker M, Holtzman DM, Tanzi RE, Vassar R, et al. Science. 2013 May 24; 340(6135):924-f.
Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models". [Science. 2013]
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Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models". [Science. 2013]
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