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
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
-
Regulation and Function of DNA and Histone Methylations
Current Pharmaceutical Design Non-steroidal Anti-inflammatory Drugs and Cyclooxygenase in Alzheimer s Disease
Current Drug Targets Right Temporal Variant Frontotemporal Dementia Misdiagnosed as Schizophrenia
Current Psychiatry Research and Reviews Variability in Reward Responsivity and Obesity: Evidence from Brain Imaging Studies
Current Drug Abuse Reviews Endothelial Dysfunction and Coronary Atherosclerosis
Current Drug Targets - Cardiovascular & Hematological Disorders Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease
Current Alzheimer Research Dual BACE-1/GSK-3β Inhibitors to Combat Alzheimer's Disease: A Focused Review
Current Topics in Medicinal Chemistry Subject Index to Volume 11
Protein & Peptide Letters Blood-Brain Barrier P-Glycoprotein Function in Neurodegenerative Disease
Current Pharmaceutical Design Cognitive Stimulation: The Evidence Base for its Application in Neurodegenerative Disease
Current Alzheimer Research Matrix Metalloproteinase Dependent Cleavage of Cell Adhesion Molecules in the Pathogenesis of CNS Dysfunction with HIV and Methamphetamine
Current HIV Research Is Human Immunodeficiency Virus-Mediated Dementia an Autophagic Defect that Leads to Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Pharmacological Interventions and Rehabilitation Approach for Enhancing Brain Self-repair and Stroke Recovery
Current Neuropharmacology S-nitrosation/Denitrosation in Cardiovascular Pathologies: Facts and Concepts for the Rational Design of S-nitrosothiols
Current Pharmaceutical Design Mitochondrial Alterations and Neuropsychiatric Disorders
Current Medicinal Chemistry Inhibition of microRNA-155 Alleviates Cognitive Impairment in Alzheimer’s Disease and Involvement of Neuroinflammation
Current Alzheimer Research Biologics and the Cardiovascular System: A Double-Edged Sword
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Tackling the Elusive Challenges Relevant to Conquering the 100-Plus Year Old Problem of Alzheimer’s Disease
Current Alzheimer Research Liver X Receptor-Mediated Gene Regulation and Cholesterol Homeostasis in Brain: Relevance to Alzheimers Disease Therapeutics
Current Alzheimer Research Nutrition, Brain Aging, and Alzheimers Disease
Current Nutrition & Food Science