Impact of amyloid β25-35 on membrane stability, energy metabolism, and antioxidant enzymes in erythrocytes.

Overview

Amyloid β25-35 (Aβ25-35) represents a neurotoxic fragment of Aβ1-40 or Aβ1-42, and is implicated in the progressive neurodegeneration in cases of the Alzheimer disease (AD). Amyloid β25-35 was shown to lyse rat erythrocytes (RBCs) of all ages, and the extent of the RBC toxicity is directly correlated with Aβ25-35 concentration and cell age. Activities of glycolytic, antioxidant, and Na(+)/K(+)-adenosine triphosphatase (ATPase) enzymes, in vivo, are significantly decreased in older RBCs as compared to the young RBCs. In vitro, Aβ25-35 reduced activities of hexokinase, phosphofructokinase, pyruvate kinase, glutathione peroxidase, and glutathione transferase and increased Na(+)/K(+)-ATPase activity; these effects are significantly greater in aged RBCs as compared to those of the younger cells. The diminution in activity of certain enzymes may determine the life span of the RBCs in vivo and may be relevant to the human AD; higher sensitivity of older RBCs to Aβ25-35 toxicity may contribute to the ultimate death of the RBCs in patients with AD.