Docosahexaenoic acid stimulates non-amyloidogenic APP processing resulting in reduced Abeta levels in cellular models of Alzheimer's disease.
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 (Abeta). DHA administration stimulated non-amyloidogenic APP processing and reduced levels of Abeta, 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 Abeta production.
Sahlin
Charlotte
C
Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
Pettersson
Frida Ekholm
FE
Nilsson
Lars N G
LN
Lannfelt
Lars
L
Johansson
Ann-Sofi
AS
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D015260:Neprilysin / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D013268:Stimulation, Chemical
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004281:Docosahexaenoic Acids; D002784:Cholesterol; D015260:Neprilysin