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Recent data suggest that cholesterol metabolism is linked to susceptibility to Alzheimer's disease (AD). However, no direct evidence has been reported linking cholesterol metabolism and the pathogenesis of AD. To test the hypothesis that amyloid beta-peptide (Abeta) deposition can be modulated by diet-induced hypercholesterolemia, we used a transgenic-mouse(More)
Clinical, epidemiological, and laboratory studies suggest that cholesterol may play a role in the pathogenesis of Alzheimer's disease (AD). Transgenic mice exhibiting an Alzheimer's beta-amyloid phenotype were treated with the cholesterol-lowering drug BM15.766 and tested for modulation of beta-amyloid levels. BM15.766 treatment reduced plasma cholesterol,(More)
The Smith-Lemli-Opitz syndrome (SLOS) is a congenital birth defect syndrome caused by a deficiency of 3beta-hydroxysterol Delta(7)-reductase, the final enzyme in the cholesterol biosynthetic pathway. The patients have reduced plasma and tissue cholesterol concentrations with the accumulation of 7-dehydrocholesterol and 8-dehydrocholesterol. Bile acid(More)
The Smith-Lemli-Opitz syndrome (SLOS) is a malformation/mental retardation syndrome resulting from an inborn error in 3beta-hydroxysteroid Delta7-reductase (DHCR7), the terminal enzyme required for cholesterol biosynthesis. Using a targeting strategy designed to virtually eliminate Dhcr7 activity, we have created a SLOS mouse model that exhibits commissural(More)
Large quantities of C27 bile alcohols hydroxylated at C-25 are excreted in the bile and urine of patients with cerebrotendinous xanthomatosis, a lipid storage disease that results from defective bile acid synthesis. The presence of both biliary and urinary bile alcohols reflects impaired bile acid synthesis. After treatment of samples with(More)
BACKGROUND The low concentration and highly hydrophobic nature of proteins in lipid raft samples present significant challenges for the sensitive and accurate proteomic analyses of lipid raft proteins. Elimination of highly enriched lipids and interfering substances from raft samples is generally required before mass spectrometric analyses can be performed,(More)
We investigated the effects of cholesterol, cholestyramine, and taurocholate feeding on steady state specific activities and mRNA levels of hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and cholesterol 7 alpha-hydroxylase in the rat. Interruption of the enterohepatic circulation of bile acids (cholestyramine feeding) increased total HMG-CoA(More)
Mice with a targeted mutation of 3beta-hydroxysterol Delta(7)-reductase (Dhcr7) that cannot convert 7-dehydrocholesterol to cholesterol were used to identify the origin of fetal sterols. Because their heterozygous mothers synthesize cholesterol normally, virtually all sterols found in a Dhcr7 knockout fetus having a Delta(7) or a Delta(8) double bond must(More)
In humans, genetic disorders affecting post-squalene cholesterol biosynthesis result in a variety of dysmorphology syndromes. One key feature of all of these is the presence of mental retardation and another is the lack of a robust genotype-phenotype correlation. Knockout mice defective in the 3beta hydroxysterol Delta7 reductase (Dhcr7), a model for the(More)