We investigated whether peroxisome proliferator-activated receptor ␥ (PPAR␥) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. Inducing expression or activating PPAR␥ using synthetic agonists of the thiazolinedione family results in a dramatic decrease in the levels of the amyloid-␤ (A␤) peptide in the conditioned medium of neuronal and non-neuronal cells. PPAR␥ does not affect expression or activity of any of the secretases involved in the generation of

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... A␤ peptide but induces a fast, cell-bound clearing mechanism responsible for the removal of the A␤ peptide from the medium. Although PPAR␥ expression is generally low in the CNS, induction of PPAR␥ expression during inflammation could be beneficial for inducing A␤ clearance. We confirm that the A␤ clearance mechanism can indeed be induced by PPAR␥ activation in primary murine-mixed glia and cortical neuronal cultures. Our results suggest that PPAR␥-controlled mechanisms should be explored further as potential drug targets for Alzheimer's disease treatment.