Microsomal prostaglandin E synthase‐1 is induced in alzheimer's disease and its deletion mitigates alzheimer's disease‐like pathology in a mouse model

Epidemiological studies have suggested that long‐term use of nonsteroidal anti‐inflammatory drugs that inhibit cyclooxygenase (COX) activity can moderate the onset or progression of Alzheimer's disease (AD). Thus it has been suggested that prostaglandin E 2 (PGE 2 ), a major end‐product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. Here we found that, among three PGES enzymes, only microsomal PGES‐1 (mPGES‐1) is induced, and its expression is associated with β‐amyloid (Aβ) plaques in the cerebral cortex in human AD patients and in Tg2576 mice, a transgenic AD mouse model. Furthermore, to investigate whether mPGES‐1 contributes to AD‐like pathology, we bred mPGES‐1‐deficient mice with Tg2576 mice. We found that mPGES‐1 deletion reduced the accumulation of microglia around senile plaques and attenuated learning impairments in Tg2576 mice. These results indicated that mPGES‐1 is induced in the AD brain and thus plays a role in AD pathology. Blockage of mPGES‐1 could form the basis for a novel therapeutic strategy for patients with AD. Inc. © 2013 Wiley Periodicals, Inc.