Abstract
Apolipoprotein E (APOE) 4 allele and sigma-1 receptor (SIGMAR1) c.5C (Q2P) polymorphisms have been acknowledged as risk factors for developing Alzheimers disease (AD). However, whether these polymorphisms influence the disease process is unclear. Therefore, two cohorts with a clinical diagnosis of AD were recruited, a postmortem confirmed Australian cohort (82 cases) from the Australian Brain Bank Network, and a Chinese cohort with detailed clinical assessments recruited through an epidemiology study in Shanghai and through the neurology department outpatients clinic of Shanghai Ruijin Hospital (330 cases). SIGMAR1 Q2P and APOE genotyping was performed on all cases. Dementia severity in the Chinese cohort was assessed using MMSE scores, and the stages of senile plaques and neurofibrillary tangles (NFT) assessed in the Australian cohort. Associations between SIGMAR1 Q2P and APOE genotypes and disease severity were assessed using SPSS. Results confirmed that APOE 4 allele associated with increased NFT stages and cognitive decline, with carriers with one APOE 2 or 3 allele often having better clinical outcomes compared to carriers with none or two 2 or 3 alleles respectively. SIGMAR1 c.5C polymorphism alone did not associate with MMSE score variability in Chinese or with pathological stages in Caucasians. However, the association studies revealed a significant genetic interaction between the APOE 4 allele and SIGMAR1 2P carriers in both populations, i.e., in APOE non 4 allele carriers, SIGMAR1 2P variant had increased cognitive dysfunction and more advanced stages of NFT. Our data demonstrate that SIGMAR1 and APOE interact to influence AD severity across ethnic populations.
Keywords: Alzheimer's disease, SIGMAR1, APOE, disease severity, genetic associations, Sigma-1 receptor, dementia syndrome, 4 allele, histopathological diagnosis, neurofibrillary tangles
Current Alzheimer Research
Title: Genetic Polymorphisms in Sigma-1 Receptor and Apolipoprotein E Interact to Influence the Severity of Alzheimers Disease
Volume: 8 Issue: 7
Author(s): Yue Huang, Lan Zheng, Glenda Halliday, Carol Dobson-Stone, Ying Wang, Hui-Dong Tang, Li Cao, Yu-Lei Deng, Gang Wang, Yu-Mei Zhang, Jian-Hua Wang, Marianne Hallupp, John Kwok and Sheng-Di Chen
Affiliation:
Keywords: Alzheimer's disease, SIGMAR1, APOE, disease severity, genetic associations, Sigma-1 receptor, dementia syndrome, 4 allele, histopathological diagnosis, neurofibrillary tangles
Abstract: Apolipoprotein E (APOE) 4 allele and sigma-1 receptor (SIGMAR1) c.5C (Q2P) polymorphisms have been acknowledged as risk factors for developing Alzheimers disease (AD). However, whether these polymorphisms influence the disease process is unclear. Therefore, two cohorts with a clinical diagnosis of AD were recruited, a postmortem confirmed Australian cohort (82 cases) from the Australian Brain Bank Network, and a Chinese cohort with detailed clinical assessments recruited through an epidemiology study in Shanghai and through the neurology department outpatients clinic of Shanghai Ruijin Hospital (330 cases). SIGMAR1 Q2P and APOE genotyping was performed on all cases. Dementia severity in the Chinese cohort was assessed using MMSE scores, and the stages of senile plaques and neurofibrillary tangles (NFT) assessed in the Australian cohort. Associations between SIGMAR1 Q2P and APOE genotypes and disease severity were assessed using SPSS. Results confirmed that APOE 4 allele associated with increased NFT stages and cognitive decline, with carriers with one APOE 2 or 3 allele often having better clinical outcomes compared to carriers with none or two 2 or 3 alleles respectively. SIGMAR1 c.5C polymorphism alone did not associate with MMSE score variability in Chinese or with pathological stages in Caucasians. However, the association studies revealed a significant genetic interaction between the APOE 4 allele and SIGMAR1 2P carriers in both populations, i.e., in APOE non 4 allele carriers, SIGMAR1 2P variant had increased cognitive dysfunction and more advanced stages of NFT. Our data demonstrate that SIGMAR1 and APOE interact to influence AD severity across ethnic populations.
Export Options
About this article
Cite this article as:
Huang Yue, Zheng Lan, Halliday Glenda, Dobson-Stone Carol, Wang Ying, Tang Hui-Dong, Cao Li, Deng Yu-Lei, Wang Gang, Zhang Yu-Mei, Wang Jian-Hua, Hallupp Marianne, Kwok John and Chen Sheng-Di, Genetic Polymorphisms in Sigma-1 Receptor and Apolipoprotein E Interact to Influence the Severity of Alzheimers Disease, Current Alzheimer Research 2011; 8 (7) . https://dx.doi.org/10.2174/156720511797633232
DOI https://dx.doi.org/10.2174/156720511797633232 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...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
-
Mechanisms of HIV Transcriptional Regulation by Drugs of Abuse
Current HIV Research The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results
Current Cardiology Reviews Chaperone-like Activity of alpha-Crystallin and Other Small Heat Shock Proteins
Current Protein & Peptide Science Analysis of Functional Brain Images Using Population-Based Probabilistic Atlas
Current Medical Imaging HspB5/αB-Crystallin: Properties and Current Progress in Neuropathy
Current Neurovascular Research Investigation of Gene Expression Pattern of 5HTR2a and MAO-A in PBMCs of Individuals Who Had Been Exposed to Air Pollution in Highly Polluted Area
Recent Patents on Inflammation & Allergy Drug Discovery Anti-α4β1 Integrin Antibodies Attenuated Brain Inflammatory Changes in a Mouse Model of Alzheimer’s Disease
Current Alzheimer Research Laminin and its Related Peptides for the Treatment of Alzheimers Disease
Current Medicinal Chemistry - Central Nervous System Agents New Anti-Thrombotic Drugs for Stroke Prevention
Current Vascular Pharmacology “Vascular Incontinence” and Normal-Pressure Hydrocephalus: Two Commonsources of Elderly Incontinence with Brain Etiologies
Current Drug Therapy Targeting Striatal Metabotropic Glutamate Receptor Type 5 in Parkinson’s Disease: Bridging Molecular Studies and Clinical Trials
CNS & Neurological Disorders - Drug Targets Daidzein and its Effects on Brain
Current Medicinal Chemistry Clozapine Safety, 40 Years Later
Current Drug Safety Drugs Used to Treat Parkinsons Disease, Present Status and Future Directions
CNS & Neurological Disorders - Drug Targets QSAR and Molecular Docking Techniques for the Discovery of Potent Monoamine Oxidase B Inhibitors: Computer-Aided Generation of New Rasagiline Bioisosteres
Current Topics in Medicinal Chemistry Polyphenols: A Diverse Class of Multi-Target Anti-HIV-1 Agents
Current Drug Metabolism Non Smoking for Successful Aging: Therapeutic Perspectives
Current Pharmaceutical Design Lipid Biomarkers in Alzheimer's Disease
Current Alzheimer Research Discovery and Optimization of Pyrazoline Derivatives As Promising Monoamine Oxidase Inhibitors
Current Topics in Medicinal Chemistry Cerebral Microinfarcts and Dementia: A Systematic Review and Metaanalysis
Current Alzheimer Research