The Neuroprotective Role of Omega-3 Fatty Acids & Potential Significance for Alzheimer’s

Effects of DHA-Rich Omega-3 Fatty Acid Supplementation on Gene Expression in Blood Mononuclear Leukocytes: The OmegAD Study
– Source: PLoS ONE, Apr 24, 2012

By Inger vedin, et al.

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Background: Dietary fish oil, rich in omega-3 fatty acids (n-3 FAs) – e.g. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) – regulate inflammatory reactions by various mechanisms, e.g. gene activation.

However, the effects of long-term treatment with DHA and EPA in humans, using genome wide techniques, are poorly described.

Hence, our aim was to determine the effects of 6 months of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells.

Methods and Findings: In the present study, blood samples were obtained from a subgroup of 16 patients originating from the randomized double-blind, placebo-controlled OmegAD study, where 174 Alzheimer disease (AD) patients received daily either 1.7 g of DHA and 0.6 g EPA or placebo for 6 months.

In blood samples obtained from 11 patients receiving n-3 FA and five placebo, expressions of approximately 8,000 genes were assessed by gene array.

Significant changes were confirmed by real-time PCR.

At 6 months, the n-3 FAs group displayed significant rises of DHA and EPA plasma concentrations, as well as up- and down-regulation of 9 and 10 genes, respectively, was noticed.

• Many of these genes are involved in inflammation regulation and neurodegeneration, e.g. CD63, MAN2A1, CASP4, LOC399491, NAIP, and SORL1

• And in ubiqutination processes, e.g. ANAPC5 and UBE2V1. [Ubiqutination processes degrade targeted proteins. “Alteration of the ubiquitination pathway” is thought to play a role in the build-up of plaques in brains of Alzheimer’s and other neurodegenerative illnesses such as Parkinson’s. ]

• Down-regulations of ANAPC5 and RHOB correlated to increases of plasma DHA and EPA levels.

Conclusions: We suggest that 6 months of dietary n-3 FA supplementation affected expression of genes that might influence inflammatory processes and could be of significance for AD.

Trial Registration: NCT00211159

Source: PLoS ONE, Apr 24, 2012. By Vedin I, Cederholm T, Freund-Levi Y, Basun H, Garlind A, Irving GF, Eriksdotter-Jonhagen M, Wahlund LO, Dahlman I, Palmblad J. Department of Medicine, and Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm; Department of Public Health and Caring Sciences, Division of Geriatrics, and Division of Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden. Authors have declared that no competing interests exist. [Email:]

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