title: Chylomicron amyloid-beta in the aetiology of Alzheimer's disease.
abstract: Alzheimer's disease is characterized by inflammatory proteinaceous deposits comprised principally of the protein amyloid-beta (Abeta). Presently, the origins of cerebral amyloid deposits are controversial, though pivotal for the prevention of Alzheimer's disease. Recent evidence suggests that in blood, Abeta may serve as a regulating apoprotein of the triglyceride-rich-lipoproteins and we have found that the synthesis of Abeta 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 Abeta in response to diets rich in saturated fats may lead to disturbances within the cerebrovasculature and exaggerated blood-to-brain delivery of circulating Abeta, thereby exacerbating amyloidosis. Consistent with this hypothesis we show that enterocytic Abeta 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.
authors.affiliation: Faculty of Health Sciences, Curtin University of Technology, ATN Centre for Metabolic Health and Fitness, Building 400, Bentley Campus, Perth, Western Australia 6102, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Takechi
authors.forename: S
authors.initials: S
authors.lastname: Galloway
authors.forename: M M S
authors.initials: MM
authors.lastname: Pallebage-Gamarallage
authors.forename: J C L
authors.initials: JC
authors.lastname: Mamo
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism*; D006801:Humans; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D002914:Chylomicrons