Several studies have shown the protective effects of dietary enrichment of various lipids in several late-onset animal models of Alzheimer's 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 Abeta 40 and 42 peptides compared to 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 in SFAs, upstream omega-3 FAs and AA.

Immunoblotting experiments and use of APP-C99 transfected Cos-7 cells suggests that FA-driven altered production of Abeta is mediated through gamma-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 Abeta and amyloid plaques in the brain, when they were fed low fat diet enriched in DHA. Our work contributes to clarify aspects of structure-activity relationships.

PMID: 20971855

See following link for full manuscript