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Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer’s disease
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  1. M Combrinck1,
  2. J Williams1,
  3. M A De Berardinis2,
  4. D Warden1,
  5. M Puopolo2,
  6. A D Smith1,
  7. L Minghetti2
  1. 1The Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology and Radcliffe Infirmary, Oxford, UK
  2. 2Istituto Superiore di Sanità, Rome, Italy
  1. Correspondence to:
 Dr Luisa Minghetti
 Department of Cell Biology and Neurosciences, Section of Degenerative and Inflammatory Neurological Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; luisa.minghetti{at}iss.it

Abstract

Background: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer’s disease are largely unknown.

Objective: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival in patients with Alzheimer’s disease.

Methods: CSF PGE2 was measured on at least three annual visits in 35 controls and 33 Alzheimer patients (26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG).

Results: Compared with controls, CSF PGE2 was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer’s disease. The median survival time of patients with higher initial PGE2 levels was five years longer than those with lower levels.

Conclusions: COX activity in Alzheimer’s disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer’s disease.

  • ADRDA, Alzheimer’s Disease and Related Disorders Association
  • CAMCOG, Cambridge cognitive assessment
  • CERAD, Consortium to Establish a Registry for Alzheimer’s Disease
  • COX, cyclo-oxygenase
  • LMEM, linear mixed effects modelling
  • MMSE, mini-mental state examination
  • NINCDS, National Institute of Neurological and Communicative Disorders and Stroke
  • NSAID, non-steroidal anti-inflammatory drug
  • OPTIMA, Oxford project to investigate memory and aging
  • PGE2, prostaglandin E2
  • Alzheimer’s disease
  • prostaglandin E2
  • cyclo-oxygenase
  • cerebrospinal fluid
  • inflammation

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Footnotes

  • Competing interests: none declared

  • Dr Combrinck’s present address: Neurology Unit, Department of Medicine, University of Cape Town, South Africa.

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