Increased Expression of Cyclooxygenases and Peroxisome Proliferator-Activated Receptor-γ in Alzheimer's Disease Brains

Abstract Recent studies suggest that inflammatory events are associated with plaque formation in the brains of patients with Alzheimer's disease (AD). Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) of these patients appears to slow the progression of disease. We assessed the occurrence of cyclooxygenases (COX-1 and -2) and peroxisome proliferator-activated receptor-γ (PPARγ) in temporal cortex from normal and AD brains using specific antibodies. In AD brains, protein levels of COX-1 were increased in both cytosolic and particulate fractions, and COX-2 protein was also increased in the particulate fraction. On the other hand, PPARγ level was increased in the cytosolic fraction but not in the particulate fraction. Thus, expression levels of COX-1, COX-2, and PPARγ may change in AD brains. In addition, several NSAIDs which are also PPARγ activators, such as indomethacin, inhibited COX-2 expression in glial cells. These results suggest that PPARγ activators have inhibitory effects on inflammatory events in AD brains.

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