Mild systemic oxidative stress in the subclinical stage of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a late-onset, progressive degenerative disorder that affects mainly the judgment, emotional stability, and memory domains. AD is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless, it is clear that oxidative stress and inflammatory pathways are among these factors. 65 elderly subjects (42 cognitively intact and 23 with probable Alzheimer's disease) were selected for this study. We evaluated erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase as well as plasma levels of total glutathione, α-tocopherol, β-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured basal expression of monocyte HLA-DR and CD-11b, as well as monocyte production of cytokines IL1-α, IL-6, and TNF-α. AD patients presented lower plasmatic levels of α-tocopherol when compared to control ones and also higher basal monocyte HLA-DR expression associated with higher IL-1α production when stimulated by LPS. These findings support the inflammatory theory of AD and point out that this disease is associated with a higher basal activation of circulating monocytes that may be a result of α-tocopherol stock depletion.

Figure 1

Representative flow cytometric analysis of whole blood samples stained with anti-CD11b-APC (right column) and anti-HLA-DR-PE (left column) monoclonal antibodies. From all events acquired in gate R1 (upper left graph), CD14-positive monocytes (gate R2, separated from CD66b-positive neutrophils in gate R3; upper right graph) were used for histogram calculation of the geometric mean fluorescence intensity (GMFI). A similar analysis was performed for the detection of fluorescent DCF in the ROS assay (histogram not shown). INT (sample from cognitively intact patient) and AD (sample from patient with probable Alzheimer's disease).

Figure 2

Representative flow cytometric detection of monocyte intracellular production of IL-1α, IL-6, and TNF-α. Monocytes were selected in a similar manner as described in Figure 1. LPS-induced production of each cytokine was determined by the percentage of events in the upper right quadrant (%URQ). Only upper quadrants are shown. INT (sample from cognitively intact patient) and AD (sample from patient with probable Alzheimer's disease).