Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 26, Issue 4, Pages 882-889Publisher
WILEY
DOI: 10.1111/j.1460-9568.2007.05719.x
Keywords
amyloid precursor protein; amyloid-beta; APP intracellular domain; polyunsaturated fatty acids; secretases
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Epidemiological studies suggest that a high intake of polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), is associated with a reduced risk of Alzheimer's disease. Here, we examined the effects of DHA on amyloid precursor protein (APP) processing in cellular models of Alzheimer's disease by analysing levels of different APP fragments, including amyloid-beta (A beta). DHA administration stimulated non-amyloidogenic APP processing and reduced levels of A beta, providing a mechanism for the reported beneficial effects of DHA in vivo. However, an increased level of APP intracellular domain was also observed, highlighting the need to increase our knowledge about the relevance of this fragment in Alzheimer's disease pathogenesis. In conclusion, our results suggest that the proposed protective role of DHA in Alzheimer's disease pathogenesis might be mediated by altered APP processing and A beta production.
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