Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1-42 levels in APPV717I transgenic mice

 In this study the authors report that acute treatment of Tg AD mice with ibuprofen or the specific PPARg agonist, pioglitazone, resulted in reduction of microglial activation, inflammatory gene expression, BACE1 levels and Abeta deposition in the brain. More specifically the data show that an acute 7 day oral treatment of 10-month-old APPV717I mice with the PPARg agonist pioglitazone or the NSAID ibuprofen resulted in a reduction in the number of activated microglia and reactive astrocytes in the hippocampus and cortex. Drug treatment reduced the expression of the proinflammatory enzymes cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS). In addition, pioglitazone and ibuprofen treatment decreased beta-secretase-1 (BACE1) mRNA and protein levels. Importantly, data showed a significant reduction of the total area and staining intensity of Abeta 1–42-positive amyloid deposits in the hippocampus and cortex.  The authors conclude that these findings demonstrate that anti-inflammatory drugs can act rapidly to inhibit inflammatory responses in the brain and negatively modulate amyloidogenesis.