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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

The Effects of Gender and CYP46 and Apo E Polymorphism on 24S-Hydroxycholesterol Levels in Alzheimers Patients Treated with Statins

Author(s): Gloria Lena Vega, Myron Weine, Heike Kolsch, Klaus von Bergmann, Reinhard Heun, Dieter Lutjohan, Anh Nguyen and Carol Moore

Volume 1, Issue 1, 2004

Page: [71 - 77] Pages: 7

DOI: 10.2174/1567205043480546


To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma levels of 24S-hydroxycholesterol in Alzheimers disease (AD) patients and to determine whether these factors contribute to the variability in responses to statin treatment. Fifty-three AD patients had measurement of plasma levels of 24S-hydroxycholesterol , plasma and lipoprotein cholesterol and genotyping of CYP46 and apo E. Thirty-nine of the subjects subsequently participated in a statin trial for 6 weeks, and had a repetition of the baseline measurements. Baseline levels of 24S-hydroxycholesterol were higher in women than in men. There was a positive and significant correlation of plasma oxysterol levels with levels of total plasma cholesterol (women: r = .72, P < .0001; men: r = .47, P = .02) and non-HDL cholesterol (women: r = .68, P < .0001; men: r = 0.51, P = .01) (and LDL cholesterol) but not HDL cholesterol levels. There was no association of CYP46 or apo E polymorphisms with plasma levels of 24S-hydroxycholesterol. AD subjects treated with statins had a similar percent reduction in lathosterol, 24S-hydroxycholesterol, total cholesterol and non-HDL (and LDL) cholesterol regardless of gender and polymorphisms of CYP46. Subjects with the ε4 / 4 polymorphism had less reduction in the ratios of 24S-hydroxycholesterol-LDL cholesterol. Women with AD had higher levels of plasma 24S-hydroxycholesterol levels than men. Women also showed a very strong correlation of plasma levels of 24S-hydroxycholesterol-to-total and non-HDL cholesterol. This may suggest that the oxysterol may be an important marker of AD risk instead of total cholesterol, as suggested by others. Polymorphisms of CYP46 or apo E do not explain levels of oxysterol or non-HDL cholesterol or the responsiveness to statin treatment in this study.

Keywords: 24S-hydroxycholesterol, CYP46 and apo E polymorphisms, statins, plasma cholesterol

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