Elevated microsomal prostaglandin-E synthase-1 in Alzheimer's disease

Background: The proinflammatory prostaglandin E, (PGE(2)) fluctuates over time in the cerebrospinal fluid of patients with Alzheimer's disease (AD), but the cerebral distribution and expression patterns of microsomal prostaglandin-E synthase (mPGES)-1 have not been compared with those of normal human brains. Methods: Middle frontal gyrus tissue from AD and age-matched control brains was analyzed by Western blot, immunofluorescence, and immunohistochemistry with mPGES-1-specific antibodies. Results: Western blotting revealed that mPGES-1 expression was significantly elevated in AD tissue. Furthermore, immunofluorescence of mPGES-1 was observed in neurons, microglia, and endothelial cells of control and AD tissue. Although mPGES-1 was consistently present in astrocytes of control tissue, it was present in only some astrocytes of AD tissue. Immunohistochemical staining suggested that mPGES-1 was elevated in pyramidal neurons of AD tissue when compared with controls. Conclusions: The results suggest that mPGES-1 is normally expressed constitutively in human neurons, microglia, astrocytes, and endothelial cells but is up-regulated in AD. (C) 2008 The Alzheimer's Association. All rights reserved.