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 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.
Combrinck
M
M
The Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology and Radcliffe Infirmary, Oxford, UK.
Williams
J
J
De Berardinis
M A
MA
Warden
D
D
Puopolo
M
M
Smith
A D
AD
Minghetti
L
L
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000453:epidemiology* / Q000401:mortality; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology*; D015232:Dinoprostone / Q000134:cerebrospinal fluid*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D015996:Survival Rate
D015232:Dinoprostone