DHA supplemented in peptamen diet offers no advantage in pathways to amyloidosis: is it time to evaluate composite lipid diet?

• Published in: PloS one Vol. 6; no. 9; p. e24094
• Main Authors: Amtul, Zareen, Keet, Mary, Wang, Lin, Merrifield, Peter, Westaway, David, Rozmahel, Richard F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08-09-2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Advertising executives; Age; AIDS; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amino acids; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Amyloid beta-protein; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Amyloid Precursor Protein Secretases - metabolism; Amyloidosis; Amyloidosis - metabolism; Amyloidosis - pathology; Amyloidosis - prevention & control; Animals; Aspartic Acid Endopeptidases - metabolism; Biochemistry; Biology; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain research; Clinical trials; Dementia; Diet; Dietary Fats - administration & dosage; Dietary Supplements; Docosahexaenoic acid; Docosahexaenoic Acids - administration & dosage; Down-Regulation - drug effects; Enzymes; Fatty acids; Fatty Acids - metabolism; Gastrointestinal diseases; Gene Expression - drug effects; Genetic engineering; HIV; Human immunodeficiency virus; Immunohistochemistry; Insulin; Insulysin - metabolism; Lipids; Low fat; Low fat diet; Medical research; Medicine; Mice; Mice, Transgenic; Neurodegenerative diseases; Nutrients; Nutrition; Nutrition research; Oligopeptides - administration & dosage; Omega 3 fatty acids; Pathogenesis; Peptides; Physiology; Plaque, Amyloid - metabolism; Potassium; Proteins; Proteolysis; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Secretase; Senile plaques; Studies; Transgenic animals; Transgenic mice; Triglycerides; Unsaturated fatty acids; Up-Regulation - drug effects; β-Amyloid; β-Site APP-cleaving enzymes; Ontario Canada; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024094

Numerous reports have documented the beneficial effects of dietary docosahexaenoic acid (DHA) on beta-amyloid production and Alzheimer's disease (AD). However, none of these studies have examined and compared DHA, in combination with other dietary nutrients, for its effects on plaque pathogenesis. Potential interactions of DHA with other dietary nutrients and fatty acids are conventionally ignored. Here we investigated DHA with two dietary regimes; peptamen (pep+DHA) and low fat diet (low fat+DHA). Peptamen base liquid diet is a standard sole-source nutrition for patients with gastrointestinal dysfunction. Here we demonstrate that a robust AD transgenic mouse model shows an increased tendency to produce beta-amyloid peptides and amyloid plaques when fed a pep+DHA diet. The increase in beta-amyloid peptides was due to an elevated trend in the levels of beta-secretase amyloid precursor protein (APP) cleaving enzyme (BACE), the proteolytic C-terminal fragment beta of APP and reduced levels of insulin degrading enzyme that endoproteolyse beta-amyloid. On the contrary, TgCRND8 mice on low fat+DHA diet (based on an approximately 18% reduction of fat intake) ameliorate the production of abeta peptides and consequently amyloid plaques. Our work not only demonstrates that DHA when taken with peptamen may have a tendency to confer a detrimental affect on the amyloid plaque build up but also reinforces the importance of studying composite lipids or nutrients rather than single lipids or nutrients for their effects on pathways important to plaque development.