期刊
ATHEROSCLEROSIS SUPPLEMENTS
卷 9, 期 2, 页码 19-25出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosissup.2008.05.010
关键词
Chylomicrons; Amyloid-beta; Alzheimer's disease; Blood-brain barrier
Alzheimer's disease is characterized by inflammatory proteinaceous deposits comprised principally of the protein amyloid-beta (A beta). Presently. the origins of cerebral amyloid deposits are controversial, though pivotal for the prevention of Alzheimer's disease. Recent evidence suggests that in blood, A may serve as a regulating apoprotein of the triglyceride-rich-lipoproteins and we have found that the synthesis of A beta in enterocytes and thereafter secretion as part of the chylomicron cascade is regulated by dietary fats. It is our contention that chronically elevated plasma levels of A beta in response to diets rich in saturated fats may lead to disturbances within the cerebrovasculature and exaggerated blood-to-brain delivery of circulating A beta, thereby exacerbating amyloidosis. Consistent with this hypothesis we show that enterocytic A beta is increased concomitant with apolipoprotein B48. Furthermore, cerebral extravasation of immunoglobulin G, a surrogate marker of plasma proteins is observed in a murine model of Alzheimer's disease maintained on a saturated-fat diet and there is diminished expression of occludin within the cerebrovasculature, an endothelial tight junction protein. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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