Abstract
Features of autoimmunity have been associated with both Alzheimers disease (AD) and with diabetes. In both diseases high levels of advanced glycation end products (AGEs) and their receptor (RAGE) have been detected in tissues and in the circulation. In addition high titers of antibodies directed against a RAGE-like peptide occur in the circulation. In this study we report the presence of auto-antibodies directed against RAGE and the cytotoxic amyloid peptide Aβ42 in plasma samples derived from four study groups. Anti-RAGE IgG titers were greatest in the AD-diabetic cohort. They were followed in decreasing order by the AD-non-diabetic cohort, the elderly diabetic cohort, and lastly by the control non-diabetic elderly cohort. The same profile of IgG differences was evident for the anti-Aβ42 titers. When all of the data were combined, there was a strong linear correlation between the RAGE and Aβ42 titers suggesting that the two peptides exist as a tight complex in plasma. Plasma IgG titers were not correlated with cognitive status except that AD and ADdiabetic participants were significantly cognitively impaired relative to the two non-AD groups. There also was no significant correlation between IgG titers and subject age, except that there was a trend for a negative slope for the AD participants and a positive slope for the control participants. In keeping with the human data, we also report that chemicallyinduced diabetes in rats was associated with high levels of AGEs, anti-RAGE-like IgGs, and anti-Aβ42-like IgGs. For non-diabetic rats, there was a clear age-dependency regarding the magnitude of the IgG levels. These data support the concept of an interrelationship between diabetes and AD. For both diseases one underlying contributing factor to cytotoxicity could be the development of an autoimmune response triggered by the presence of AGEs and amyloid peptides.
Keywords: Diabetes, anti-RAGE, AD-non-diabetic cohort, plasma IgG levels, anti-Ab42 IgG markers
Current Alzheimer Research
Title: Autoimmunity in Alzheimers Disease as Evidenced by Plasma Immunoreactivity Against RAGE and Aβ42: Complication of Diabetes
Volume: 3 Issue: 3
Author(s): Shyamala Mruthinti, Rosann F. Schade, Dean U. Harrell, Nidhi K. Gulati, S. Swamy-Mruthinti, Gregory P. Lee and Jerry J. Buccafusco
Affiliation:
Keywords: Diabetes, anti-RAGE, AD-non-diabetic cohort, plasma IgG levels, anti-Ab42 IgG markers
Abstract: Features of autoimmunity have been associated with both Alzheimers disease (AD) and with diabetes. In both diseases high levels of advanced glycation end products (AGEs) and their receptor (RAGE) have been detected in tissues and in the circulation. In addition high titers of antibodies directed against a RAGE-like peptide occur in the circulation. In this study we report the presence of auto-antibodies directed against RAGE and the cytotoxic amyloid peptide Aβ42 in plasma samples derived from four study groups. Anti-RAGE IgG titers were greatest in the AD-diabetic cohort. They were followed in decreasing order by the AD-non-diabetic cohort, the elderly diabetic cohort, and lastly by the control non-diabetic elderly cohort. The same profile of IgG differences was evident for the anti-Aβ42 titers. When all of the data were combined, there was a strong linear correlation between the RAGE and Aβ42 titers suggesting that the two peptides exist as a tight complex in plasma. Plasma IgG titers were not correlated with cognitive status except that AD and ADdiabetic participants were significantly cognitively impaired relative to the two non-AD groups. There also was no significant correlation between IgG titers and subject age, except that there was a trend for a negative slope for the AD participants and a positive slope for the control participants. In keeping with the human data, we also report that chemicallyinduced diabetes in rats was associated with high levels of AGEs, anti-RAGE-like IgGs, and anti-Aβ42-like IgGs. For non-diabetic rats, there was a clear age-dependency regarding the magnitude of the IgG levels. These data support the concept of an interrelationship between diabetes and AD. For both diseases one underlying contributing factor to cytotoxicity could be the development of an autoimmune response triggered by the presence of AGEs and amyloid peptides.
Export Options
About this article
Cite this article as:
Mruthinti Shyamala, Schade F. Rosann, Harrell U. Dean, Gulati K. Nidhi, Swamy-Mruthinti S., Lee P. Gregory and Buccafusco J. Jerry, Autoimmunity in Alzheimers Disease as Evidenced by Plasma Immunoreactivity Against RAGE and Aβ42: Complication of Diabetes, Current Alzheimer Research 2006; 3 (3) . https://dx.doi.org/10.2174/156720506777632899
DOI https://dx.doi.org/10.2174/156720506777632899 |
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
-
Antioxidant Capacities of Flavones and Benefits in Oxidative-Stress Related Diseases
Current Topics in Medicinal Chemistry Insights Into Early and Rapid Effects of Statin Therapy after Coronary Interventions
Current Pharmaceutical Design Therapeutic and Protective Potential of Mesenchymal Stem Cells, Pharmaceutical Agents and Current Vaccines Against COVID-19
Current Stem Cell Research & Therapy Concerning Arterial Hypertension, Homocysteine and Paraoxonase-1
Current Hypertension Reviews Alkaptonuria, Ochronosis and Ochronotic Arthropathy in Mainland France and the Reunion Island. A Report of Clinical and Molecular Findings in 29 Patients
Current Rheumatology Reviews Non-Communicable Diseases and Adherence to Mediterranean Diet
Endocrine, Metabolic & Immune Disorders - Drug Targets Predictors of Ominous Outcome in Infants who Undergo Cardiac Surgery and Cardiopulmonary By-Pass: S100B Protein
CNS & Neurological Disorders - Drug Targets Targeting Vascular Redox Biology Through Antioxidant Gene Delivery: A Historical View and Current Perspectives
Recent Patents on Cardiovascular Drug Discovery Current Applications of Artificial Neural Networks in Biochemistry with Emphasis on Cancer Research
Current Biochemical Engineering (Discontinued) Risk Scores for Patients with Chest Pain: Evaluation in the Emergency Department
Current Cardiology Reviews Aliskiren: A New Drug for an Old Problem
Cardiovascular & Hematological Agents in Medicinal Chemistry Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Current Drug Targets Anti-Inflammatory Properties of Drugs from saffron crocus
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Effects of Verbascoside Administration on the Blood Parameters and Oxidative Status in Jennies and Their Suckling Foals: Potential Improvement of Milk for Human Use
Endocrine, Metabolic & Immune Disorders - Drug Targets Synthesis and Biological Evaluation of Atorvastatin Derivatives as Novel HMG-CoA Reductase Inhibitors
Letters in Drug Design & Discovery Cardiovascular Magnetic Resonance Imaging: State of the Art
Current Cardiology Reviews Lower Serum Indirect Bilirubin Levels are Inversely Related to Carotid Intima-Media Thickness Progression
Current Neurovascular Research The Effect of Antihypertensive Agents on Insulin Sensitivity, Lipids and Haemostasis
Current Vascular Pharmacology Role of Antioxidants, Essential Fatty Acids, Carnitine, Vitamins, Phytochemicals and Trace Elements in the Treatment of Diabetes Mellitus and its Chronic Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Effects of Statins on Bone Markers, Bone Mineral Density and Fractures. Possible Role in Osteoporosis Treatment
Current Pharmaceutical Analysis