Cyclooxygenase-1 and -2 in the different stages of Alzheimer's disease pathology

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of beta amyloid (Abeta) protein and the formation of neurofibrillary tangles. In addition, there is an increase of inflammatory proteins in the brains of AD patients. Epidemiological studies, indicating that non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk of developing AD, have encouraged the study on the role of inflammation in AD. The best-characterized action of most NSAIDs is the inhibition of cyclooxygenase (COX). The expression of the constitutively expressed COX-1 and the inflammatory induced COX-2 has been intensively investigated in AD brain and different disease models for AD. Despite these studies, clinical trials with NSAIDs or selective COX-2 inhibitors showed little or no effect on clinical progression of AD. The expression levels of COX-1 and COX-2 change in the different stages of AD pathology. In an early stage, when low-fibrillar Abeta deposits are present and only very few neurofibrillary tangles are observed in the cortical areas, COX-2 is increased in neurons. The increased neuronal COX-2 expression parallels and colocalizes with the expression of cell cycle proteins. COX-1 is primarily expressed in microglia, which are associated with fibrillar Abeta deposits. This suggests that in AD brain COX-1 and COX-2 are involved in inflammatory and regenerating pathways respectively. In this review we will discuss the role of COX-1 and COX-2 in the different stages of AD pathology. Understanding the physiological and pathological role of cyclooxygenase in AD pathology may facilitate the design of therapeutics for the treatment or prevention of AD.

Original languageEnglish
Pages (from-to)1419-27
Number of pages9
JournalCurrent pharmaceutical design
Issue number14
Publication statusPublished - 2008


  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cell Cycle Proteins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase Inhibitors
  • Humans
  • Inflammation
  • Journal Article
  • Neurons
  • Research Support, Non-U.S. Gov't
  • Review

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