Elevated CSF prostaglandin E-2 levels in patients with probable AD

Objective: To determine CSF eicosanoid concentrations and brain cyclo-oxyge nase activity in AD patients and age-matched control subjects. Background: Nonsteroidal anti-inflammatory drugs may benefit AD patients by inhibiting cyclo-oxygenases and thereby reducing prostaglandin (PG) production or oxid ant stress in the CNS. Methods: CSF eicosanoid and F-2-isoprostane (IsoP) l evels were determined in seven probable AD patients and seven age-matched c ontrol subjects. Cyclo-oxygenase activity was determined in microsomes prep ared from the hippocampus of 10 definite AD patients and 8 age-matched cont rol subjects. All measurements were made using gas chromatography/mass spec trometry. Results: CSF concentrations of prostaglandin (PG) E-2 were increa sed fivefold (p < 0.01) and 6-keto-PGF(1 alpha) was decreased fourfold (p < 0.01) in probable AD patients. There was no change in total CSF eicosanoid concentration in probable AD patients. CSF F-2-IsoP, a quantitative marker of lipid peroxidation in vivo, was increased in probable AD patients (p < 0.05). Cyclo-oxygenase activity in the hippocampus from definite AD patient s was not different from age-matched control subjects. Conclusions: These d ata suggest that cyclo-oxygenase activity may not contribute significantly to CNS oxidative damage in AD. Increased CSF PGE, concentration in probable AD patients suggest that cyclo-oxygenase inhibitors may benefit AD patient s by limiting PG production.