An FDA-approved drug called bexarotene counters many of the effects of Alzheimer’s disease in mouse models, researchers report. The build-up of protein fragments called amyloid-beta is a key feature of the disease; everyone’s brain produces amyloid-beta, but in healthy individuals, enzymes break the fragments down, with help from a protein called ApoE. Paige Cramer and colleagues knew that bexarotene activates a protein that helps switch on the ApoE gene, and they hypothesized that the drug might therefore enhance the clearance of amyloid-beta in the brain. They gave the drug to mice engineered to have an Alzheimer’s-like condition and observed that levels of the protein fragments in the mice’s brains dropped substantially within just a few days. The mice also showed improvements in their cognitive, social and olfactory performance. Bexarotene, also known as Targretin, is currently used to treat a form of skin cancer and has a favorable safety profile, the authors note. The drug activates the nuclear receptor protein known as RXR, which binds one of two other nuclear receptors, PPAR and LXR. These receptor pairs then activate the transcription of the ApoE gene.
Article #14: "ApoE-directed Therapeutics Rapidly Clear β-amyloid and Reverse Deficits in AD Mouse Models," by P.E. Cramer; D.W. Wesson; C.Y.D. Lee; J.C. Karlo; A.E. Zinn; Brad T. Casali; G.E. E. Landreth at Case Western Reserve University School of Medicine in Cleveland, OH; J.R. Cirrito; J.L. Restivo; W.D. Goebel at Washington University School of Medicine in St. Louis, MO; D.W. Wesson; D.A. Wilson at Nathan Kline Institute for Psychiatric Research in Orangeburg, NY; D.W. Wesson; D.A. Wilson at New York University School of Medicine in Orangeburg, NY; M.J. James; K.R. Brunden at University of Pennsylvania in Philadelphia, PA.