The essential role of lipids in Alzheimer’s disease

In the absence of efficient diagnostic and therapeutic tools, Alzheimer’s disease (AD) is a major public
health concern due to longer life expectancy in the Western countries. Although the precise cause of AD
is still unknown, soluble b-amyloid (Ab) oligomers are considered the proximate effectors of the synaptic
injury and neuronal death occurring in the early stages of AD. Ab oligomers may directly interact with
the synaptic membrane, leading to impairment of synaptic functions and subsequent signalling
pathways triggering neurodegeneration. Therefore, membrane structure and lipid status should be
considered determinant factors in Ab-oligomer-induced synaptic and cell injuries, and therefore AD
progression. Numerous epidemiological studies have highlighted close relationships between AD inci-
dence and dietary patterns. Among the nutritional factors involved, lipids significantly influence AD
pathogenesis. It is likely that maintenance of adequate membrane lipid content could prevent the
production of Ab peptide as well as its deleterious effects upon its interaction with synaptic membrane,
thereby protecting neurons from Ab-induced neurodegeneration. As major constituents of neuronal
lipids, n-3 polyunsaturated fatty acids are of particular interest in the prevention of AD valuable diet
ingredients whose neuroprotective properties could be essential for designing preventive nutrition-
based strategies. In this review, we discuss the functional relevance of neuronal membrane features with
respect to susceptibility to Ab oligomers and AD pathogenesis, as well as the prospective capacities of
lipids to prevent or to delay the disease.