Journal of Biological Chemistry
Volume 286, Issue 8, 25 February 2011, Pages 6100-6107
Journal home page for Journal of Biological Chemistry

Neurobiology
Structural Insight into the Differential Effects of Omega-3 and Omega-6 Fatty Acids on the Production of Aβ Peptides and Amyloid Plaques*

https://doi.org/10.1074/jbc.M110.183608Get rights and content
Under a Creative Commons license
open access

Several studies have shown the protective effects of dietary enrichment of various lipids in several late-onset animal models of Alzheimer Disease (AD); however, none of the studies has determined which structure within a lipid determines its detrimental or beneficial effects on AD. High-sensitivity enzyme-linked immunosorbent assay (ELISA) shows that saturated fatty acids (SFAs), upstream omega-3 FAs, and arachidonic acid (AA) resulted in significantly higher secretion of both Aβ 40 and 42 peptides compared with long chain downstream omega-3 and monounsaturated FAs (MUFA). Their distinct detrimental action is believed to be due to a structural template found in their fatty acyl chains that lack SFAs, upstream omega-3 FAs, and AA. Immunoblotting experiments and use of APP-C99-transfected COS-7 cells suggest that FA-driven altered production of Aβ is mediated through γ-secretase cleavage of APP. An early-onset AD transgenic mouse model expressing the double-mutant form of human amyloid precursor protein (APP); Swedish (K670N/M671L) and Indiana (V717F), corroborated in vitro findings by showing lower levels of Aβ and amyloid plaques in the brain, when they were fed a low fat diet enriched in DHA. Our work contributes to the clarification of aspects of structure-activity relationships.

Aging
Alzheimer Disease
Fatty Acid
Lipid
Lipid Structure
Micfatty Acid
Amyloid
Transgenic e
COS-7 Cells
Plaques

Cited by (0)

*

Grants from the FP5 framework LipiDiet project QLK-2002-172, the FP7 project LipiDiDiet 211696, London and Middlesex Alzheimer Association (Marion and Chester Fish Alzheimer Disease Research Grant), the Canadian Institutes of Health Research (MOP49546) (to R. F. R.), and the Alexander von Humboldt and Ontario Mental Health Foundation Awards (to Z. A.) funded this research.