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From the Departments of Biochemistry (B.C. Crews and Dr. Marnett), Medicine (Drs. Roberts and Morrow), Pathology (Dr. Montine and K.R. Sidell), and Pharmacology (Drs. Montine, Roberts, and Morrow), the A.B. Hancock Jr. Memorial Laboratory for Cancer Research (Dr. Marnett), Vanderbilt University Medical Center, Nashville, TN; and the Departments of Pathology and Neurology and the Sanders Brown Center on Aging (Dr. Markesbery), University of Kentucky Medical Center, Lexington, KY.
Address correspondence and reprint requests to Dr. Thomas J. Montine, Department of Pathology, Vanderbilt University Medical Center, C-3321A Medical Center North, Nashville, TN 37232.
OBJECTIVE: To determine CSF eicosanoid concentrations and brain cyclo-oxygenase 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 oxidant stress in the CNS.
METHODS: CSF eicosanoid and F2-isoprostane (IsoP) levels were determined in seven probable AD patients and seven age-matched control subjects. Cyclo-oxygenase activity was determined in microsomes prepared from the hippocampus of 10 definite AD patients and 8 age-matched control subjects. All measurements were made using gas chromatography/mass spectrometry.
RESULTS: CSF concentrations of prostaglandin (PG) E2 were increased fivefold (p < 0.01) and 6-keto-PGF1
was decreased fourfold (p < 0.01) in probable AD patients. There was no change in total CSF eicosanoid concentration in probable AD patients. CSF F2-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 patients was not different from age-matched control subjects.
CONCLUSIONS: These data suggest that cyclo-oxygenase activity may not contribute significantly to CNS oxidative damage in AD. Increased CSF PGE2 concentration in probable AD patients suggest that cyclo-oxygenase inhibitors may benefit AD patients by limiting PG production.
Key words: CSF—AD—Prostaglandins—Cyclo-oxygenase.
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