ALZHEIMER A-BETA NEUROTOXICITY - PROMOTION BY ANTICHYMOTRYPSIN, APOE4- INHIBITION BY A-BETA-RELATED PEPTIDES

Two inflammation-associated proteins found in the Alzheimer amyloid de posits-alpha(1)-antichymotrypsin (ACT) and apolipoprotein E4 (apoE4)-h ave been shown to be genetic risk factors for the development of Alzhe imer's disease and to promote the polymerization of the A beta peptide into amyloid filaments in vitro. In the present study, we show that A CT and apoE4 increase the neurotoxicity of the A beta peptide in paral lel with their promotion of filament formation. Preincubation of ACT o r apoE4 with small A beta-related peptides, or of apoE4 with apoE2, ab rogated their subsequent ability to promote both the formation and the neurotoxicity of A beta filaments. These results indicate that ACT an d apoE4 may play a stimulatory role in the formation of neurotoxic amy loid in Alzheimer's disease, and that their amyloid promoting activity can be blocked by inhibitory peptides.