Therapeutics: Peroxisome proliferation activated receptor (PPAR) α; retinoid X receptor (RXR)

In vitro and mouse studies suggest agonists of PPARα and its co-activator RXR could help treat AD. In a mouse model of AD, PPARα knockout increased β amyloid (Aβ) deposition and decreased survival compared with normal PPARα expression. In hippocampal neurons from normal mice, the PPARα agonist gemfibrozil or the RXR agonist retinoic acid increased levels of the Aβ-downregulating protease ADAM metallopeptidase domain 10 (ADAM10) and decreased Aβ levels, whereas the compounds did not have these effects in PPARα-knockout mice. Next steps include clinical testing of gemfibrozil as monotherapy and in combination with retinoic acid in AD patients...