Elevated CSF prostaglandin E2 levels in patients with probable AD.
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-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.


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.
Montine
T J
TJ
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Sidell
K R
KR
Crews
B C
BC
Markesbery
W R
WR
Marnett
L J
LJ
Roberts
L J
LJ
Morrow
J D
JD
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000818:Animals; D001921:Brain / Q000201:enzymology; D015232:Dinoprostone / Q000134:cerebrospinal fluid*; D015777:Eicosanoids / Q000134:cerebrospinal fluid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D051379:Mice; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000134:cerebrospinal fluid; D012016:Reference Values
D015777:Eicosanoids; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone