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Elevated CSF prostaglandin E2 levels in patients with probable AD.
T J Montine1, K R Sidell, B C Crews
1Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Neurology
|October 26, 1999
Summary
Alzheimer's disease (AD) patients show increased prostaglandin E2 in cerebrospinal fluid (CSF), suggesting cyclo-oxygenase inhibitors may help by limiting prostaglandin production. Brain cyclo-oxygenase activity was not elevated in AD.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may benefit Alzheimer's disease (AD) patients.
- NSAIDs work by inhibiting cyclo-oxygenases, potentially reducing prostaglandin production or central nervous system (CNS) oxidant stress.
Purpose of the Study:
- To determine cerebrospinal fluid (CSF) eicosanoid concentrations and brain cyclo-oxygenase activity in AD patients.
- To compare these levels with age-matched control subjects.
Main Methods:
- CSF eicosanoid and F2-isoprostane (IsoP) levels were measured in probable AD patients and controls using gas chromatography/mass spectrometry.
- Cyclo-oxygenase activity was assessed in hippocampal microsomes from definite AD patients and controls.
Main Results:
- CSF prostaglandin E2 (PGE2) concentrations were significantly increased in probable AD patients.
- CSF 6-keto-PGF1alpha levels were decreased, while F2-isoprostane levels (a marker of lipid peroxidation) were increased in probable AD patients.
- No significant difference in cyclo-oxygenase activity was found in the hippocampus of definite AD patients compared to controls.
Conclusions:
- Cyclo-oxygenase activity may not be a major contributor to CNS oxidative damage in AD.
- Elevated CSF PGE2 suggests that cyclo-oxygenase inhibitors could be beneficial for AD patients by reducing prostaglandin synthesis.