Alzheimer's disease and n-3 polyunsaturated fatty acids: Beneficial effects and possible molecular pathways involved

Elderly dementia is rising dramatically in Western countries. In particular, the irreversible memory impairment, continuous cognitive decline and behavioural disturbances present in Alzheimer's disease patients make this neurodegenerative disorder highly disabiliting. Different epidemiological studies and experimental researches on transgenic mouse models suggest that dietary consumption of the two main long chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may modify the risk and progression of this neurodegenerative disorder. In addition, decreased blood levels of n-3 PUFAs have been associated with this disease in humans. In particular, among n-3 PUFAs, DHA is known to be the most prevalent PUFA in neuronal tissues. Animals specifically deficient in dietary n-3 PUFAs have shown to possess low DHA content in their membranes and impaired learning ability. Moreover, studies on non breast-fed infants have shown that DHA added to formula milk augments the levels of this fatty acid in infant blood improving their mental development. The potential mechanisms by which these fatty acids may function in normal neuronal activity and in neurodegenerative disease prevention and treatment are not well understood, even though these topics are now under investigation in numerous laboratories. In this review the current knowledge about the molecular mechanisms by which n-3 PUFAs are thought to regulate neuronal function, survival and degeneration will be examined. Since the pathological neuronal lesions of Alzheimer disease have been pathogenetically related to alterations of inflammatory and survival/apoptotic responses, molecular modulation of these pathways by n-3 PUFAs in neuronal tissues and cells will be particularly considered.