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.
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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
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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
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