Do Red Blood Cell-β-Amyloid Interactions Alter Oxygen Delivery in Alzheimer’s Disease?

Abstract

Oxygen delivery requires that Red Blood Cells (RBCs) must be deformable to pass through the microcirculation. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by abnormal extracellular deposition of β-amyloid peptide (Aβ) and neuronal loss. We have analyzed RBC morphology in blood from subjects with AD and found that >15% of the RBCs are elongated as compared to 5.9% in normal controls (p<0.0001). To determine whether these morphology changes can be associated with the greater exposure of RBCs to Aβ in AD subjects, we investigated the in vitro effect ofAb fibrils on blood.Morphological analysis of RBCs treated with Aβ_1-40 or Aβ_1-42 fibrils show 8.6% or 11.1% elongated cells, respectively. In contrast, only 2.9% or 1.3% of RBCs are elongated when blood is treated with buffer or mock fibrils generated from Aβ_42-1. Elongated RBCs are expected to be less deformable. This prediction is consistent with our earlier studies showing impaired deformability of RBCs treated with Aβ fibrils. An additional factor previously reported by us, expected to impair the flow of RBCs through the microcirculation is their adherence to endothelial cells (ECs) when Aβ_1-40 fibrils are bound to either RBCs or ECs. This factor would be more pronounced in AD subjects with elevated levels of Aβ on the vasculature. These results suggest that Aβ interactions with RBCs in AD subjects can result in impaired oxygen transport and delivery, which will have important implications for AD.