Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are of benefit in Alzheimer’s disease
by virtue of their anti-inflammatory actions, ability to modulate neural function, including neurotransmission,
membrane fluidity, ion channel, enzyme regulation and gene expression. EPA, DHA, and ω-6 arachidonic acid
(AA) form precursors to anti-inflammatory compounds: lipoxins, resolvins, protectins and maresins that suppress
leukocyte migration and activation, inhibit NF-κB activation, production of pro-inflammatory cytokines tumor
necrosis factor-α and interleukin-6, free radical generation, and enhance endothelial nitric oxide generation and
augment the healing process. In animal models, the protective action of EPA and DHA against Alzheimer’s
disease correlated with increased formation of lipoxins, resolvins, protectins and maresins. EPA, DHA and AA
stimulate neurite outgrowth by activating syntaxin 3 that is specifically involved in fast calcium-triggered
exocytosis of neurotransmitters. SNAP25 (synaptosomal-associated protein of 25 kDa), a syntaxin partner
implicated in neurite outgrowth, interacted with syntaxin 3 only in the presence of AA that allowed the formation
of the binary syntaxin 3-SNAP 25 complex. AA stimulated syntaxin 3 to form the ternary SNARE complex
(soluble N-ethylmaleimide-sensitive factor attachment protein receptor), which is needed for the fusion of
plasmalemmal precursor vesicles into the cell surface membrane that leads to membrane fusion that facilitates
neurite outgrowth. These results imply that EPA, DHA, and AA when given in optimal amounts are of benefit in
the prevention and treatment of Alzheimer’s disease. PUFAs enhance the concentrations of neurotrophic factors
in the brain that may provide additional protection to neurons. Thus, PUFAs by themselves or their stable
synthetic analogues could be of benefit in Alzheimer’s disease and other neurodegenerative diseases.
Keywords: Polyunsaturated fatty acids, Alzheimer’s disease, lipoxins, protectins, resolvins, maresins, syntaxin, free
radicals, nitric oxide, inflammation, cytokines, tumor necrosis factor.
