Document Detail


Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: Implications for dementia risk.
MedLine Citation:
PMID:  20430703     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Amyloid-beta (Abeta) is secreted as an apolipoprotein of nascent triglyceride-rich lipoproteins (TRL) derived from both liver and intestine, but is better recognized as the principal protein component of senile plaque in subjects with Alzheimer's disease. Recent studies suggest that exaggerated exposure to plasma Abeta can compromise cerebrovascular integrity, resulting thereafter in blood to brain delivery of plasma proteins including TRL-Abeta. Parenchymal deposits of Abeta show significant immunoreactivity to apolipoprotein B (apo B), consistent with the notion of lipoprotein-Abeta entrapment. In wild type mice chronically fed physiologically relevant diets, saturated fats (SFA) enhance chylomicron-Abeta concomitant with disturbances in blood-brain barrier integrity. Similarly, dietary cholesterol promotes cerebrovascular extravasation of apo B lipoprotein-Abeta. In this study, we investigated the effects of Atorvastatin, Pravastatin and Probucol on dietary-fat induced disturbances in BBB function. Atorvastatin, a lipid soluble HMG-CoA reductase inhibitor prevented SFA induced parenchymal extravasation of apo B-Abeta at 28 days when incorporated into the diet at 20mg/kg. In contrast, Pravastatin a water soluble agent had no effect on BBB integrity at an equivalent dose. In cholesterol supplemented mice, Probucol maintained BBB function and extravasation of apo B-Abeta was not evident. The findings suggest that some lipid-modulating agents may be effective in ameliorating the negative effects of saturated fats and cholesterol on cerebrovascular integrity.
Authors:
Menuka M S Pallebage-Gamarallage; Ryusuke Takechi; Virginie Lam; Susan Galloway; Satvinder Dhaliwal; John C L Mamo
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Publication Detail:
Type:  Journal Article     Date:  2010-04-28
Journal Detail:
Title:  Atherosclerosis. Supplements     Volume:  11     ISSN:  1878-5050     ISO Abbreviation:  Atheroscler Suppl     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100973461     Medline TA:  Atheroscler Suppl     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  49-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Faculty of Health Sciences, Curtin University of Technology and ATN Centre for Metabolic Health and Fitness, Perth, WA, Australia.
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