β-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin

The therapeutic effects of fish oil, rich in omega-3 fatty acids (FA), and curcumin in dementia and Alzheimer’s disease (AD) hypothesized by several preclinical studies, was recently contradicted by clinical evidence. The Rotterdam study, which involved ~6000 participants aged greater than or equal to 55 and monitored over 10 years for mortality and major morbidity, clearly demonstrated that omega-3 FA supplementation did not reduce the risk of developing dementia and AD in the elderly. Specifically, individuals with a higher fish intake had a risk of developing dementia or AD similar to that of those who usually did not eat fish (Devore et al., 2009). Parallel results were obtained by the Canadian Study of Health and Aging, in which the association between erythrocyte membrane concentration of omega-3 FA and the incidence of dementia and AD was evaluated in 650 patients aged greater than or equal to 65 (Kröger et al., 2009). In this study, no evidence of a reduced risk of dementia or AD among subjects with higher levels of plasma omega-3 FA was found over a follow-up period of about 5 years. Similar negative results were obtained in AD patients treated with curcumin. In a randomized, placebo-controlled, double-blind clinical trial, curcumin (1-4 g/day for 6 months) failed to improve cognitive performance in patients suffering from mild-to-moderate AD and had no effect on pro-inflammatory biomarkers like serum amyloid-beta-peptide and isoprostanes (Baum et al., 2008). Based on these findings, the use of omega-3 FA and/or curcumin to preserve cognitive function in the elderly seems not to have any scientific basis.

References

Baum L et al. (2008) Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 28:110-113.

Devore EE, Grodstein F, van Rooij FJ, Hofman A, Rosner B, Stampfer MJ, Witteman JC, Breteler MM (2009) Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk. Am J Clin Nutr 90:170- 176.

Kröger E, Verreault R, Carmichael PH, Lindsay J, Julien P, Dewailly E, Ayotte P, Laurin D (2009) Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging. Am J Clin Nutr 90:184-192.