Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer’s disease

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 E 2 (PGE 2 ), in relation to cognitive decline and survival in patients with Alzheimer’s disease. Methods: CSF PGE 2 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 PGE 2 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 PGE 2 levels was five years longer than those with lower levels. Conclusions: COX activity in Alzheimer’s disease varies with stage of the disease. PGE 2 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.