Red cell perturbations by amyloid β-protein

Amyloid beta-protein (Abeta) accumulation in brain is thought to be important in causing the neuropathology of Alzheimer's disease (AD). Abeta interactions with both neurons and microglial cells play key roles in AD. Since vascular deposition of Abeta is also implicated in AD, the interaction of red cells with these toxic aggregates gains importance. However, the effects of A interactions with red blood cells are less well understood. Synthetic amyloid beta-protein (1-40) was labeled with biotin and preincubated at 37 degreesC for 4, 14 and 72 h to produce fibrils. Flow cytometry was used to study the binding of these fibrils to red cells. The amyloid fibrils had a high affinity for the red cell with increased binding for the larger fibrils produced by longer preincubation. Bovine serum albumin (BSA) did not reverse the binding, but actually resulted in a more efficient binding of the Abeta fibrils to the red cells. The interaction of Abeta with red cells increased the mean cell volume and caused the cells to become more spherical. This effect was greater for the longer fibrils. At the same time the interaction of Abeta with red cells produced an increase in their fluorescence measured after 16-h incubation at 37 degreesC. This increase in fluorescence is attributed to the formation of fluorescent heme degradation products. The effect of prior hemoglobin oxidation, catalase inhibition and glutathione peroxidase inhibition indicated that the amyloid-induced oxidative damage to the red cell involved hydrogen peroxide-induced heme degradation. These results suggest that amyloid interactions with the red cell may contribute to the pathology of AD. Published by Elsevier B.V.