Albumin protects human red blood cells against Aβ25-35-induced lysis more effectively than ApoE

Inhibition of the lysis of human red blood cells (RBCs) exposed to amyloid peptide Abeta(25-35) is an in vitro model for screening natural and synthetic substances potentially protective against amyloid damage. In this system, human serum and a component, namely apolipoprotein E (apoE), completely prevent RBC lysis. This report demonstrates that albumin, another serum component, is 8 -fold more protective: a concentration of 12.5 mug/ml protects RBCs against 20 muM-Abeta(25-35), and prevents the formation of fibrillar Abeta(25-35) aggregates stainable by Congo Red. The biological relevance of these findings is suggested by the following: (1) a large fraction (similar to90%) of circulating Abeta(1-42) is bound to albumin; (2) albumin immunoreactivity is present in brain amyloid plaques; and (3) incubation of Abeta with albumin rapidly decreases detectable levels of free Abeta suggesting epitope masking. The results add new and important functional consequences to the amyloid-albumin relationship and imply that experimental systems investigating Abeta cytotoxicity should consider the protective interaction of albumin.