In Alzheimer's disease (AD), beta-amyloid (A beta) is deposited in extracellular matrices, initiating an inflammatory response and compromising cellular integrity. Epidemiological evidence and studies in animal models provide strong evidence that high-saturated-fat and/or cholesterol-rich diets exacerbate cerebral amyloidosis, although the mechanisms for this are unclear. A contains hydrophobic domains and is normally bound to lipid-associated chaperone proteins. In previous studies, we have put forward the notion that All is a regulatory component of postprandial lipoproteins (i.e., chylomicrons) and that aberrations in kinetics may be a contributing risk factor for AD. To explore this further, in this study, we utilized an immunohistochemical approach to determine if A beta or its precursor protein is expressed in epithelial cells of the small intestine - the site of chylomicron biogenesis. Wild-type mice were fed a low-fat or a high-fat dietary regime and sacrificed, and their small intestines were isolated. We found that, in mice fed low-fat chow, substantial A beta/precursor protein was found exclusively in absorptive epithelial cells of the small intestine. In contrast, no A beta/precursor protein was found in epithelial cells when mice were fasted for 65 h. In addition, we found that a high-fat feeding regime strongly stimulates epithelial cell A beta/precursor protein concentration. Our findings are consistent with the notion that A may serve as a regulatory apolipoprotein of postprandial lipoproteins. (c) 2007 Published by Elsevier Inc.