Red cell interactions with amyloid-β_1-40 fibrils in a murine model

Vascular amyloidosis in Alzheimer's disease (AD) results in the exposure of red blood cells to β-amyloid fibrils (Aβ). The potential in vivo ramifications of this exposure have been investigated by injecting Aβ_1-40 alone or Aβ-bound mouse red blood cells into the circulation of C57BL/6 mice. Results indicate that when Aβ_1-40 is injected alone, a transient uptake of the fibrils by red blood cells occurs in vivo. When Aβ-bound red blood cells were injected, β-amyloid is rapidly removed from these cells in vivo. Double-labeling experiments indicate that while some of the red blood cells bound to Aβ_1-40 are removed from circulation, a major fraction of these cells remain in circulation even after Aβ is removed. Immunohistochemistry of murine tissue samples obtained after sacrificing the animals suggests that within 1 h after injection of Aβ_1-40 or Aβ-bound red blood cells, Aβ is found in spleen phagocytes and liver Kupffer cells. Heme staining further indicates that the binding of Aβ_1-40 to red blood cells enhances red cell phagocytosis by the spleen.