Document Detail

Structural insight into the differential effects of omega-3 and omega-6 fatty acids on the production of Abeta peptides and amyloid plaques.
MedLine Citation:
PMID:  20971855     Owner:  NLM     Status:  MEDLINE    
Several studies have shown the protective effects of dietary enrichment of various lipids in several late-onset animal models of Alzheimer Disease (AD); however, none of the studies has determined which structure within a lipid determines its detrimental or beneficial effects on AD. High-sensitivity enzyme-linked immunosorbent assay (ELISA) shows that saturated fatty acids (SFAs), upstream omega-3 FAs, and arachidonic acid (AA) resulted in significantly higher secretion of both Aβ 40 and 42 peptides compared with long chain downstream omega-3 and monounsaturated FAs (MUFA). Their distinct detrimental action is believed to be due to a structural template found in their fatty acyl chains that lack SFAs, upstream omega-3 FAs, and AA. Immunoblotting experiments and use of APP-C99-transfected COS-7 cells suggest that FA-driven altered production of Aβ is mediated through γ-secretase cleavage of APP. An early-onset AD transgenic mouse model expressing the double-mutant form of human amyloid precursor protein (APP); Swedish (K670N/M671L) and Indiana (V717F), corroborated in vitro findings by showing lower levels of Aβ and amyloid plaques in the brain, when they were fed a low fat diet enriched in DHA. Our work contributes to the clarification of aspects of structure-activity relationships.
Zareen Amtul; Markus Uhrig; Richard F Rozmahel; Konrad Beyreuther
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-21     Completed Date:  2011-04-14     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6100-7     Citation Subset:  IM    
Zentrum für Molekulare Biologie Heidelberg, University of Heidelberg, Heidelberg, Germany.
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MeSH Terms
Alzheimer Disease / genetics,  metabolism*,  pathology
Amyloid / genetics,  metabolism*
Amyloid Precursor Protein Secretases / genetics,  metabolism
Amyloid beta-Protein Precursor / biosynthesis*,  genetics
Brain / metabolism,  pathology
COS Cells
Cercopithecus aethiops
Disease Models, Animal
Fatty Acids, Omega-3 / metabolism,  pharmacology*
Fatty Acids, Omega-6 / metabolism,  pharmacology*
Mice, Mutant Strains
Peptides / genetics,  metabolism*
Grant Support
MOP49546//Canadian Institutes of Health Research
Reg. No./Substance:
0/APP protein, human; 0/Amyloid; 0/Amyloid beta-Protein Precursor; 0/Fatty Acids, Omega-3; 0/Fatty Acids, Omega-6; 0/Peptides; EC 3.4.-/Amyloid Precursor Protein Secretases

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