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• W2010508749 abstract "Cholesterol and 24S-hydroxycholesterol are involved in the pathogenesis of Alzheimer's disease (AD). Increased serum cholesterol concentrations have been detected in patients with AD. 24S-Hydroxycholesterol is the primary cholesterol elimination product of the brain and possesses neurotoxic properties in vitro. The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol, cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons. Concentrations of 24S-hydroxycholesterol in cerebrospinal fluid (CSF) and serum differ significantly between AD patients and non-demented subjects. To test the hypothesis if polymorphisms in the CYP46 gene might influence the function of the respective enzyme and thus cholesterol metabolism in the human brain, we screened for polymorphisms in 114 AD patients and 144 healthy controls. Two intronic single nucleotide polymorphisms were observed and their allelic distribution was investigated. In our study sample, carriers of the C allele of the IVS3+43C --> T polymorphism were more prevalent in the group of AD patients than in healthy controls, while another IVS2-150A --> G polymorphism did not show a significant association with AD. The CC genotype of the IVS3+43C --> T polymorphism was associated with an increased 24S-hydroxycholesterol/cholesterol ratio in the CSF of AD patients. Our results indicate that the CYP46 gene locus may predispose to AD by increasing the 24S-hydroxycholesterol/cholesterol ratio in the brain." @default.
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• W2010508749 date "2002-09-01" @default.
• W2010508749 modified "2023-10-14" @default.
• W2010508749 title "Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease" @default.
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• W2010508749 doi "https://doi.org/10.1038/sj.mp.4001109" @default.
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