and may be a promising therapy for Alzheimer’s disease. Several groups have observed that prolonged treatment with PPARγ agonists can reduce Alzheimer’s disease pathology, demonstrating its potential therapeutic efficacy [102,136,137]. In addition to reducing plaques, the PPARγ agonist pioglitazone increased mRNA levels of the M2 marker YM1 [137] as well as the scavenger receptor CD36 [102]. Recently, activation of the retinoid X receptor (RXR), which forms a heterodimer with PPARγ, was implicated as a promising therapeutic treatment for Alzheimer’s disease. Landreth’s group [103] demonstrated that treatment with the FDA-approved RXR agonist bexarotene reduced CNS Aβ levels and improved cognition in an Alzheimer’s disease mouse model [103]. Interestingly, PPARγ treatment has been demonstrated to polarize human monocytes to an M2 state [138], which further supports the idea that manipulating proinflammatory M1 microglia to an M2 phenotype is a potentially viable therapeutic option.
