Skin cancer drug reverses Alzheimer's in mice
cnn.com
cnn.com
>The morning concluded with a talk by Gary Landreth from Case Western Reserve University, Cleveland, Ohio. Landreth has worked for several years to identify ApoE-directed therapeutics. As one of the genes involved in cholesterol homeostasis, ApoE is regulated transcriptionally by PPARγ and liver X receptors, which both form heterodimers with the retinoid X receptor (RXR). Working with APP transgenic mice, Landreth found that an RXR agonist, bexarotene, induces brain ApoE quickly and robustly. This induction precedes a rapid decline in brain amyloid, an increase in plaque-clearing microglia, and improvements in cognitive performance. Landreth noted that bexarotene is an FDA-approved chemotherapeutic that readily crosses the blood-brain barrier and has minimal side effects, most of which are associated with its action on lipid homeostasis. Hence, this drug minimally represents a test of the role of Aβ in AD and, maximally, may represent an AD therapeutic, he suggested. The presentation elicited a discussion of the utility of the drug in ApoE4-positive individuals, i.e., if ApoE4 represents a toxic gain of function, then bexarotene-induced increases in ApoE4 may exacerbate AD. Landreth noted that the drug has been in use for roughly a decade without reports of cognitive deficits as a side effect.