Docosahexaenoic Acid Reduces Amyloid-β

The effect of supplementation with the omega 3 polyunsaturated fatty acid (n-3 PUFA) docosahexaenoic acid (DHA) on membrane composition and amyloidβ1−42 (Aβ42) secretion was studied in human amyloidβ protein precursor-transfected Chinese Hamster Ovary (CHO) cells. Twenty-four hour incubation with a range of DHA concentrations resulted in a dosedependent increase in membrane DHA and eicosapentaenoic acid content and a decrease in arachidonic acid content. In addition, DHA supplementation caused a dose-dependent reduction in the secreted A β42 levels and resulted in a 4–8 fold decrease in extracellular prostaglandin E 2 (PGE2) levels. Tocopherol, which was added to DHA to prevent oxidation, may have contributed to the effect of DHA, since it slightly decreased extracellular A β42 and PGE2 levels when given alone. The addition of selective COX-2 inhibitors Celebrex and curcumin to the culture medium resulted in a significant and comparable inhibition of PGE 2 release, but did not inhibit A β42 secretion, and even significantly increased A β42 production in this cell system. Together, the present data show that, whereas both DHA and COX-2 inhibitors may reduce PGE 2 production, only DHA in the presence of tocopherol significantly reduced A β42 production and concurrently changed membrane lipid composition in CHO cells. It is concluded that in this in vitro setting DHA reduced Aβ42 secretion through membrane-related, but not PGE 2-related mechanisms.