Decreased prostaglandin synthesis in postmortem cerebral cortex from patients with Alzheimer's disease.
The syntheses of prostaglandin (PG) F2 alpha, E2 and D2, and thromboxane (TX) B2 from [14C]arachidonic acid were studied in frontal cortex of human control and Alzheimer's disease (AD) brains using the microsomal fractions. Under the assay conditions employed, it was found that the major metabolite of [14C]arachidonic acid was PGE2 accounting for 63% of total prostanoid production; PGF2 alpha accounted for 21.5%, TXB2 for 9%, and PGD2 for 6.5%. When AD samples were compared to control samples, microsomal PG synthesis was significantly decreased, with reduced production of PGE2, PGF2 alpha and PGD2. Such decreases in AD brain seem unrelated to age, sex, postmortem delay and, as far as could be determined, antemortem state. In both control and Alzheimer groups, a history of anti-inflammatory therapy seemed to correlate with increased PG synthesis.
Wong
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Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
McGeer
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McGeer
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EG
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005972:Glutaminase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D011180:Postmortem Changes; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013929:Thromboxane B2 / Q000096:biosynthesis
D002250:Carbon Radioisotopes; D011453:Prostaglandins; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015237:Dinoprost; D002795:Choline O-Acetyltransferase; D005972:Glutaminase; D015232:Dinoprostone; D015230:Prostaglandin D2