dha supplemented in peptamen diet offers no advantage in pathways to amyloidosis is it time to evaluate composite lipid dietdha补充peptamen饮食中没有提供优势途径淀粉样变是时候来评估复合脂质饮食.pdfVIP

DHA Supplemented in Peptamen Diet Offers No Advantage in Pathways to Amyloidosis: Is It Time to Evaluate Composite Lipid Diet? 1,3 ¤ 1,3 3 2 4 1,3 Zareen Amtul * , Mary Keet , Lin Wang , Peter Merrifield , David Westaway , Richard F. Rozmahel 1 Department of Biochemistry, University of Western Ontario, London, Ontario, Canada, 2 Department of Anatomy Cell Biology, University of Western Ontario, London, Ontario, Canada, 3 Lawson Health Research Institute, London, Ontario, Canada, 4 Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada Abstract 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, T