Neuroprotective effects of DHA in Alzheimer’s disease models

Alzheimer’s disease (AD) is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ) may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3) in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i) regulation of the expression of potentially protective genes, (ii) activation of antiinflammatory pathways, (iii) modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases