Abstract
Almost 2% of the population of western industrialized countries are affected by Alzheimers disease (AD). Nevertheless the pathogenetic process leading to this neurodegenerative disease is widely unknown. Thus, we focus on novel pathophysiological aspects of AD. We hypothesize that AD patients reveal increased levels of peripheral blood mononuclear cells (PBMCs) expressing proinflammatory (COX-2, TNF-α, CD40), proapoptotic (PARP-1), adhesionrelevant (CD38) or AD associated (C99, BACE1, Presenilin-1) proteins as well as elevated proinflammatory biochemical plasma parameters. Therefore, PBMCs of AD patients and age-matched control subjects were studied by two color fluorescence- activated cell sorter (FACS) analysis. Furthermore, concentration of plasma oxidized low-density lipoprotein (oxLDL) and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). We found a significantly increased percentage of TNF-α, COX-2, PARP-1, CD38, C99 or presenilin-1 positive PBMCs in AD patients compared with healthy subjects. FACS analyses revealed that the percentage of C99 or presenilin-1 positive PBMCs, which also express TNF-α, COX-2, PARP-1 or CD38 is also increased in AD patients. Additionally, AD patients had significantly increased plasma oxLDL and TNF-α levels. Furthermore, we found positive correlations between plasma oxLDL or TNF-α concentrations and the percentage of TNFα+, COX-2+ or PARP-1+, as well as PS-1+, C99+ or BACE+ PBMCs. Our findings suggest that immunocytological investigations, based on immunophenotyping of AD relevant proteins combined with measurement of proinflammatory, proapoptotic and adhesion-relevant proteins in PBMCs may provide more insight into the pathophysiology of AD.
Keywords: Alzheimer, inflammation, oxLDL, PBMC
Current Alzheimer Research
Title: Novel Systemic Markers for Patients with Alzheimer Disease? – A Pilot Study
Volume: 5 Issue: 4
Author(s): Stefan S. Kassner, Gabriel A. Bonaterra, Elmar Kaiser, Wulf Hildebrandt, Jurgen Metz, Johannes Schroder and Ralf Kinscherf
Affiliation:
Keywords: Alzheimer, inflammation, oxLDL, PBMC
Abstract: Almost 2% of the population of western industrialized countries are affected by Alzheimers disease (AD). Nevertheless the pathogenetic process leading to this neurodegenerative disease is widely unknown. Thus, we focus on novel pathophysiological aspects of AD. We hypothesize that AD patients reveal increased levels of peripheral blood mononuclear cells (PBMCs) expressing proinflammatory (COX-2, TNF-α, CD40), proapoptotic (PARP-1), adhesionrelevant (CD38) or AD associated (C99, BACE1, Presenilin-1) proteins as well as elevated proinflammatory biochemical plasma parameters. Therefore, PBMCs of AD patients and age-matched control subjects were studied by two color fluorescence- activated cell sorter (FACS) analysis. Furthermore, concentration of plasma oxidized low-density lipoprotein (oxLDL) and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). We found a significantly increased percentage of TNF-α, COX-2, PARP-1, CD38, C99 or presenilin-1 positive PBMCs in AD patients compared with healthy subjects. FACS analyses revealed that the percentage of C99 or presenilin-1 positive PBMCs, which also express TNF-α, COX-2, PARP-1 or CD38 is also increased in AD patients. Additionally, AD patients had significantly increased plasma oxLDL and TNF-α levels. Furthermore, we found positive correlations between plasma oxLDL or TNF-α concentrations and the percentage of TNFα+, COX-2+ or PARP-1+, as well as PS-1+, C99+ or BACE+ PBMCs. Our findings suggest that immunocytological investigations, based on immunophenotyping of AD relevant proteins combined with measurement of proinflammatory, proapoptotic and adhesion-relevant proteins in PBMCs may provide more insight into the pathophysiology of AD.
Export Options
About this article
Cite this article as:
Kassner S. Stefan, Bonaterra A. Gabriel, Kaiser Elmar, Hildebrandt Wulf, Metz Jurgen, Schroder Johannes and Kinscherf Ralf, Novel Systemic Markers for Patients with Alzheimer Disease? – A Pilot Study, Current Alzheimer Research 2008; 5 (4) . https://dx.doi.org/10.2174/156720508785132253
DOI https://dx.doi.org/10.2174/156720508785132253 |
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
-
Differential Regulation of Neurotoxin in HIV Clades: Role of Cocaine and Methamphetamine
Current HIV Research <i>Larrea tridentata</i> and its Biological Activities
Current Topics in Medicinal Chemistry In Silico Approach to Finding New Active Compounds from Histone Deacetylase (HDAC) Family
Current Pharmaceutical Design Flavones from Root of Scutellaria Baicalensis Georgi: Drugs of the Future in Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Metal Ions and Metal Complexes in Alzheimer’s Disease
Current Pharmaceutical Design The Function and Regulation of BMP6 in Various Kinds of Stem Cells
Current Pharmaceutical Design Targeting Vesicle Trafficking: An Important Approach to Cancer Chemotherapy
Recent Patents on Anti-Cancer Drug Discovery Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Fatty Acid Synthase: A Target for the Reversal of Liver Steatosis
Current Enzyme Inhibition Adult Stem Cells and Biocompatible Scaffolds as Smart Drug Delivery Tools for Cardiac Tissue Repair
Current Medicinal Chemistry Genetic Surgery - A Right Strategy to Attack Cancer
Current Gene Therapy The Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP): A New Rodent Model to Test Palliative and Neuroprotective Agents for Parkinsons disease
Current Pharmaceutical Design Resveratrol, a Phytochemical Inducer of Multiple Cell Death Pathways: Apoptosis, Autophagy and Mitotic Catastrophe
Current Medicinal Chemistry Ewing’s Sarcoma Cancer Stem Cell Targeted Therapy
Current Stem Cell Research & Therapy Therapeutic Strategies for Alzheimer's and Parkinson's Diseases by Means of Drug Delivery Systems
Current Medicinal Chemistry Ligand-Targeted Liposomes for Cancer Treatment
Current Drug Delivery Potential Benefits of Glitazones for Cancer and Vascular Disease
Current Drug Therapy TRP Channels in Vascular Disorders
Current Topics in Medicinal Chemistry Sarcosine-Based Glycine Transporter Type-1 (GlyT-1) Inhibitors Containing Pyridazine Moiety: A Further Search for Drugs with Potential to Influence Schizophrenia Negative Symptoms
Current Pharmaceutical Design Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance
Anti-Cancer Agents in Medicinal Chemistry