Amyloid β Levels in Human Red Blood Cells

Abstract

Amyloid β-peptide (Aβ) is hypothesized to play a key role by oxidatively impairing the capacity of red blood cells (RBCs) to deliver oxygen to the brain. These processes are implicated in the pathogenesis of Alzheimer's disease (AD). Although plasma Aβ has been investigated thoroughly, the presence and distribution of Aβ in human RBCs are still unclear. In this study, we quantitated Aβ40 and Aβ42 in human RBCs with ELISA assays, and provided evidence that significant amounts of Aβ could be detected in RBCs and that the RBC Aβ levels increased with aging. The RBC Aβ levels increased with aging. On the other hand, providing an antioxidant supplement (astaxanthin, a polar carotenoid) to humans was found to decrease RBC Aβ as well as oxidative stress marker levels. These results suggest that plasma Aβ40 and Aβ42 bind to RBCs (possibly with aging), implying a pathogenic role of RBC Aβ. Moreover, the data indicate that RBC Aβ40 and Aβ42 may constitute biomarkers of AD. As a preventive strategy, therapeutic application of astaxanthin as an Aβ-lowering agent in RBCs could be considered as a possible anti-dementia agent.Trial RegistrationControlled-Trials.com ISRCTN42483402

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

“…Aβ40 and Aβ42 were detected also in RBCs where their levels were found to be about 8-and 14-times higher than those in plasma, respectively [67]. Exposure of RBCs exposed to Aβ on the luminal surface of cerebral microvessels induces the erythrocytes' adhesion to endothelial cells and affects endothelial functionality [68].…”

“…Exposure of RBCs exposed to Aβ on the luminal surface of cerebral microvessels induces the erythrocytes' adhesion to endothelial cells and affects endothelial functionality [68]. In addition, bounding of Aβ to RBCs impairs the capacity of RBCs for delivering oxygen thereby facilitating AD [65][66][67][68][69]. It was shown that oxidative stress and ROS production in RBC membranes was induced particularly by copper-bound Aβ [65].…”

Docosahexaenoic acid: one molecule diverse functions

“…Together, these studies suggest that Ab plays a key role in the blood and oxidatively impairs the function of RBCs, which is important for adequate O 2 supply to the brain. Kiko et al [120] reported that human RBC-Ab 1-40 and -Ab 1-42 levels increased with aging and imply a pathogenic role for RBC-Ab. RBC membranes in AD patients are injured by unavoidable exposure to Ab [120].…”

“…Kiko et al [120] reported that human RBC-Ab 1-40 and -Ab 1-42 levels increased with aging and imply a pathogenic role for RBC-Ab. RBC membranes in AD patients are injured by unavoidable exposure to Ab [120]. The reasoning is that once amyloid b peptides (Abs) of Alzheimer's disease build in the blood circulation, they are capable of binding RBCs and inducing hemolysis.…”

Studies Targeting α-Glucosidase Inhibition, Antiangiogenic Effects, and Lipid Modification Regulation: Background, Evaluation, and Challenges in the Development of Food Ingredients for Therapeutic Purposes

“…In accord with this hypothesis, we found recently evidence that A is indeed present in human RBCs. 59) Based on these findings, we are currently collecting blood samples from living AD subjects to investigate further the oxidative and pathogenic roles of RBC A and the suitability of RBC A as a biomarker for AD. On the other hand, it is well recognized that one of the major physiological activities of carotenoids is their antioxidant action and their protective effect against lipid peroxidation in biological membranes.…”