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

J Neurosci Res. 2013 Jul;91(7):909-19. doi: 10.1002/jnr.23217. Epub 2013 Mar 29.


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 E2 (PGE2 ), 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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Case-Control Studies
  • Cerebral Cortex / enzymology*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Enzymologic / genetics
  • Humans
  • Intramolecular Oxidoreductases / deficiency*
  • Intramolecular Oxidoreductases / genetics
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Prostaglandin-E Synthases


  • Amyloid beta-Protein Precursor
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Ptges protein, mouse