Abstract
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
Current Alzheimer Research
Title: The Effects of Gender and CYP46 and Apo E Polymorphism on 24S-Hydroxycholesterol Levels in Alzheimers Patients Treated with Statins
Volume: 1 Issue: 1
Author(s): Gloria Lena Vega, Myron Weine, Heike Kolsch, Klaus von Bergmann, Reinhard Heun, Dieter Lutjohan, Anh Nguyen and Carol Moore
Affiliation:
Keywords: 24S-hydroxycholesterol, CYP46 and apo E polymorphisms, statins, plasma cholesterol
Abstract: 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.
Export Options
About this article
Cite this article as:
Vega Lena Gloria, Weine Myron, Kolsch Heike, Bergmann von Klaus, Heun Reinhard, Lutjohan Dieter, Nguyen Anh and Moore Carol, The Effects of Gender and CYP46 and Apo E Polymorphism on 24S-Hydroxycholesterol Levels in Alzheimers Patients Treated with Statins, Current Alzheimer Research 2004; 1 (1) . https://dx.doi.org/10.2174/1567205043480546
DOI https://dx.doi.org/10.2174/1567205043480546 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer’s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Radiopharmaceuticals in Neurological and Psychiatric Disorders
Current Clinical Pharmacology State Dissociation, Human Behavior, and Consciousness
Current Topics in Medicinal Chemistry Towards Environmental Construct Validity in Animal Models of CNS Disorders: Optimizing Translation of Preclinical Studies
CNS & Neurological Disorders - Drug Targets Long-Term Follow-Up of Patients Immunized with AN1792: Reduced Functional Decline in Antibody Responders
Current Alzheimer Research P2X7 Receptors: Channels, Pores and More
CNS & Neurological Disorders - Drug Targets Bioactive Fish Fatty Acids: Health Effects and Their Use as Functional Food Ingredients
Current Nutrition & Food Science Pharmacological Applications of Antioxidants: Lights and Shadows
Current Drug Targets Preparation and Evaluation of Gliptin Liposomes for Targetting Ocular Region in Neurodegeneration
Nanoscience & Nanotechnology-Asia Whole Brain Atrophy and Sample Size Estimate via Iterative Principal Component Analysis for Twelve-month Alzheimer's Disease Trials
Neuroscience and Biomedical Engineering (Discontinued) Secondary Degeneration of White Matter Tract following Basal Ganglia Infarction: A Longitudinal Diffusion Tensor Imaging Study
Current Medical Imaging Adverse Events of Proton Pump Inhibitors: Potential Mechanisms
Current Drug Metabolism Cardiovascular Risk Factors in Chronic Inflammatory Rheumatic Diseases: Modern Assessment and Diagnosis
Current Vascular Pharmacology Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets General Anesthetics in Brain Injury: Friends or Foes?
Current Pharmaceutical Design Involvement of Advanced Glycation End-products (AGEs) in Alzheimers Disease
Current Alzheimer Research Potential Therapeutic Effects of Exogenous Ketone Supplementation for Type 2 Diabetes: A Review
Current Pharmaceutical Design Sleep Related Disorders in the Elderly: An Overview
Current Respiratory Medicine Reviews Plasma Gelsolin: Function, Prognostic Value, and Potential Therapeutic Use
Current Protein & Peptide Science Methylated MicroRNA Genes of the Developing Murine Palate
MicroRNA Effectiveness of a Standardized and Specific Follow-Up in Memory Centers in Patients with Alzheimer’s Disease
Current Alzheimer Research