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Novel Systemic Markers for Patients with Alzheimer Disease? - A Pilot Study

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Almost 2% of the population of western industrialized countries are affected by Alzheimer's 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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Keywords: Alzheimer; PBMC; inflammation; oxLDL

Document Type: Research Article

Publication date: August 1, 2008

More about this publication?
  • Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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