In vitro apolipoprotein E protects human red blood cells against lysis induced by amyloid-beta (Aβ) fragment 25-35

Mattson et al.(9) demonstrated lysis of human red blood cells (RBC) exposed to ain, yloidpeptide Abeta(25-35), new experimental model for amyloid-beta toxicity. Lysis resulted from pore formation in the RBC membranes and was completely prevented by concurrent exposure to Congo red. We demonstrate that human serum, purified ApoE from human plasma, and recombinant isoforms of ApoE neutralize the Abeta(25-35) cytotoxicity: the E2 and E4 isoforms were marginally more effective than E3. Second, we demonstrate that abeta(25-35) forms fibrils in the reaction mixtures using electron-microscopy, Together these results suggest than the RBC model might be useful in preliminary identification of natural and synthetic substances able to protect against amyloid-beta cytotoxic effects due to fibrillar Such compounds would be candidate molecules for testing in neuronal systems.