Author:
Pallebage-Gamarallage Menuka M.,Galloway Susan,Johnsen Russell,Jian Le,Dhaliwal Satvinder,Mamo John C. L.
Abstract
Dietary cholesterol may influence Alzheimer's disease risk, because it regulates the synthesis of amyloid-β. It was recently demonstrated in enterocytes of wild-type mice that intracellular amyloid-β expression is enhanced in response to a high-fat diet made up of SFA and cholesterol. Intestinally derived amyloid-β may be associated with postprandial lipoproteins in response to dietary fats and could be a key regulator in chylomicron metabolism. The present study was designed to investigate the role of cholesterol in modulating amyloid-β abundance in enterocytes. Wild-type mice were fed a low-fat diet supplemented with 2 % (w/w) cholesterol. The effects of cholesterol absorption inhibition and cholesterol biosynthesis inhibition utilising ezetimibe and atorvastatin, respectively, were also studied. Quantitative immunohistochemistry was utilised to determine enterocytic amyloid-β homeostasis. We found that enterocytic amyloid-β concentration was significantly attenuated in mice fed the 2 % (w/w) cholesterol diet. However, blocking cholesterol absorption reversed the cholesterol-feeding effect. Consistent with a suppressive effect of cholesterol on enterocytic amyloid-β abundance, atorvastatin, an inhibitor of cholesterol biosynthesis, enhanced amyloid-β. However, providing exogenous cholesterol abolished the atorvastatin-induced effect. In contrast to the suppression of enterocytic amyloid-β by dietary cholesterol, mice fed a diet enriched in SFA had markedly greater abundance. Collectively, the findings suggest that exogenous and endogenous cholesterol reduce amyloid-β concentration in enterocytes by suppressing production, or enhancing secretion associated with postprandial lipoproteins. Intestinally derived amyloid-β will contribute to the pool of plasma protein and may influence cerebral amyloid homeostasis by altering the bi-directional transfer across the blood–brain barrier.
Publisher
Cambridge University Press (CUP)
Subject
Nutrition and Dietetics,Medicine (miscellaneous)
Cited by
16 articles.
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