Authors: Vega G.L.; Weine M.; Kolsch H.; Bergmann K.v.o.n.; Heun R.; Lutjohan D.; Nguyen A.; Moore C.

Source: Current Alzheimer Research, Volume 1, Number 1, February 2004 , pp. 71-77(7)

Publisher: Bentham Science Publishers

Abstract:

To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma levels of 24S-hydroxycholesterol in Alzheimer's 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 4 / 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

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567205043480546

Affiliations: 1: University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390-9052, USA

Publication date: 2004-02-01

More about this publication?

• Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

Related content

• In this: publication
• By this: publisher
• In this Subject: Neurology & Psychiatry ,  Pathology
• By this author: Vega G.L. ;  Weine M. ;  Kolsch H. ;  Bergmann K.v.o.n. ;  Heun R. ;  Lutjohan D. ;  Nguyen A. ;  Moore C.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers