Elevated CSF prostaglandin E2 levels in patients with probable AD

• Published in: Neurology Vol. 53; no. 7; pp. 1495 - 1498
• Main Authors: MONTINE, T. J, SIDELL, K. R, CREWS, B. C, MARKESBERY, W. R, MARNETT, L. J, ROBERTS, L. J, MORROW, J. D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 22-10-1999
• Subjects: Aged; Alzheimer Disease - cerebrospinal fluid; Animals; Biological and medical sciences; Brain - enzymology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dinoprostone - cerebrospinal fluid; Eicosanoids - cerebrospinal fluid; Gas Chromatography-Mass Spectrometry; Humans; Medical sciences; Mice; Middle Aged; Neurology; Prostaglandin-Endoperoxide Synthases - cerebrospinal fluid; Reference Values; Human; Prostaglandin-endoperoxide synthase; Nervous system diseases; Prostaglandin; Enzyme; Alzheimer disease; Arachidonic acid derivatives; Prostaglandin E2; Exploration; Cerebrospinal fluid; Cerebral disorder; Central nervous system disease; Degenerative disease; Oxidoreductases
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/wnl.53.7.1495

To determine CSF eicosanoid concentrations and brain cyclo-oxygenase activity in AD patients and age-matched control subjects.
Nonsteroidal anti-inflammatory drugs may benefit AD patients by inhibiting cyclo-oxygenases and thereby reducing prostaglandin (PG) production or oxidant stress in the CNS.
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.
CSF concentrations of prostaglandin (PG) E2 were increased fivefold (p < 0.01) and 6-keto-PGF1alpha 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.
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.