Abstract
It was suggested that the gene encoding for sorLa, (SORL1) may affect Alzheimer's disease (LOAD) through a female-specific mechanism. The aims of this study were to confirm the role of gender in modulating the association between SORL1 and LOAD and to ascertain the influence of SORL1 on cognitive impairment, neuropsychiatric symptoms (BPSD) and secretion of pro-inflammatory cytokines.
Ninety six outpatients with LOAD and 120 unrelated controls were genotyped for APOE and three SNPs at the 5' end of SORL1(intron 6): SNP 8 (rs668387); SNP 9 (rs68902); SNP 10 (rs641120). Clinical evaluation was made with the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). ELISPOT assays were used to measure pro-inflammatory cytokine (TNF-alpha; IL-6; IL-1beta; IFN-gamma) production in peripheral blood mononuclear cell (PBMC) supernatant from AD patients. SORL1 SNPs were not associated with LOAD in overall sample. Instead the G-alleles at SNPs 9 (p=0.015) and 10 (p=0.015) and the CGG haplotype (p=0.02) were associated with LOAD in the women subgroup. The TAA haplotype was marginally protective in AD patients being associated with lower BPSD scores (p=0.01). The same haplotype was also associated with higher IL-1beta (p=0.01) production. These genetic effects were not modified by APOE4 allele and controlled for illness duration and treatment. In conclusion, SORL1 does not appear to be a major risk factor for LOAD. Its contribution could be underestimated in our small sample. Sex-specific factors could modulate the association between SORL1 and AD. The influence of SORL1 variants on production of inflammatory cytokines warrants further investigation.Keywords: SORL1, gender, Alzheimer, psychosis, inflammatory cytokines
Current Alzheimer Research
Title:Effects of SORL1 Gene on Alzheimer's Disease. Focus on Gender, Neuropsychiatric Symptoms and Pro-Inflammatory Cytokines
Volume: 10 Issue: 2
Author(s): Antonis Mailis, Alessandro Serretti, Anastasios Kalofoutis, Diana De Ronchi, Costantine R.Soldatos, Martina Balestri, Agnese Marsano, Gianluigi Forloni, Sara Batelli, Paolo Olgiati, Evangelia Stamouli, Ioannis Liappas, Christina Piperi, Aikaterini Zisaki, Letizia Polito, Serena Rodilossi, Diego Albani and Antonis Politis
Affiliation:
Keywords: SORL1, gender, Alzheimer, psychosis, inflammatory cytokines
Abstract: It was suggested that the gene encoding for sorLa, (SORL1) may affect Alzheimer's disease (LOAD) through a female-specific mechanism. The aims of this study were to confirm the role of gender in modulating the association between SORL1 and LOAD and to ascertain the influence of SORL1 on cognitive impairment, neuropsychiatric symptoms (BPSD) and secretion of pro-inflammatory cytokines.
Ninety six outpatients with LOAD and 120 unrelated controls were genotyped for APOE and three SNPs at the 5' end of SORL1(intron 6): SNP 8 (rs668387); SNP 9 (rs68902); SNP 10 (rs641120). Clinical evaluation was made with the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). ELISPOT assays were used to measure pro-inflammatory cytokine (TNF-alpha; IL-6; IL-1beta; IFN-gamma) production in peripheral blood mononuclear cell (PBMC) supernatant from AD patients. SORL1 SNPs were not associated with LOAD in overall sample. Instead the G-alleles at SNPs 9 (p=0.015) and 10 (p=0.015) and the CGG haplotype (p=0.02) were associated with LOAD in the women subgroup. The TAA haplotype was marginally protective in AD patients being associated with lower BPSD scores (p=0.01). The same haplotype was also associated with higher IL-1beta (p=0.01) production. These genetic effects were not modified by APOE4 allele and controlled for illness duration and treatment. In conclusion, SORL1 does not appear to be a major risk factor for LOAD. Its contribution could be underestimated in our small sample. Sex-specific factors could modulate the association between SORL1 and AD. The influence of SORL1 variants on production of inflammatory cytokines warrants further investigation.Export Options
About this article
Cite this article as:
Mailis Antonis, Serretti Alessandro, Kalofoutis Anastasios, De Ronchi Diana, R.Soldatos Costantine, Balestri Martina, Marsano Agnese, Forloni Gianluigi, Batelli Sara, Olgiati Paolo, Stamouli Evangelia, Liappas Ioannis, Piperi Christina, Zisaki Aikaterini, Polito Letizia, Rodilossi Serena, Albani Diego and Politis Antonis, Effects of SORL1 Gene on Alzheimer's Disease. Focus on Gender, Neuropsychiatric Symptoms and Pro-Inflammatory Cytokines, Current Alzheimer Research 2013; 10 (2) . https://dx.doi.org/10.2174/1567205011310020005
DOI https://dx.doi.org/10.2174/1567205011310020005 |
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
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
- 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
-
Obesity and Cardiovascular Physiology: Impact of some Pharmacological Agents
Current Vascular Pharmacology Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction
Current Medicinal Chemistry Vascular Cognitive Disorder: A Diagnostic and Pharmacological Treatment Updating
Current Psychopharmacology Effect of Antipsychotic Drugs on Cerebrovascular Morbidity and Mortality: A Systematic Review
Current Drug Therapy Editorial (Thematic Issue: The Monocyte/Macrophage in the Pathogenesis of AIDS: The Next Frontier for Therapeutic Intervention in the CNS and Beyond: Part I)
Current HIV Research Developments in HIV Neuropathogenesis
Current Pharmaceutical Design The Over-Under on the Misdiagnosis of Bipolar Disorder: A Systematic Review
Current Psychiatry Reviews A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase
Current Medicinal Chemistry Treatment Approaches in Elderly Patients with Head and Neck Cancer
Anti-Cancer Agents in Medicinal Chemistry Demonstration of Advanced Data Mining Tools for Optimization of Pellets Employing Modified Extrusion-pelletization Technique
Current Drug Therapy Cyclooxygenases Regulation by Estradiol on Endothelium
Current Pharmaceutical Design Advanced Nanomedicines for the Treatment and Diagnosis of Myocardial Infarction and Heart Failure
Current Drug Targets Nanomedicine and its Potential for the Treatment of Alzheimer’s Disease
Current Nanomedicine Adalimumab
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Arachidonate Cascade in the Intensive Insulin Therapy for Critically Ill Patients with Sepsis: Roles of Prostaglandins on Hyperglycemia-Impaired Immunity
Letters in Drug Design & Discovery Targeting New Pharmacological Approaches for Alzheimer’s Disease: Potential for Statins and Phosphodiesterase Inhibitors
CNS & Neurological Disorders - Drug Targets Markers of Systemic Inflammation in Obstructive Sleep Apnea Syndrome
Current Respiratory Medicine Reviews Improvement of Microscopic MR Imaging of Amyloid Plaques with Targeting and Non-Targeting Contrast Agents
Current Medical Imaging Magnesium Lithospermate B Extracted from Salvia Miltiorrhiza, A Potential Substitute for Cardiac Glycosides
Mini-Reviews in Organic Chemistry Patterns of Self-Medication with Medicinal Plants and Related Adverse Events - A South American Survey
Current Drug Safety