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.