Alzheimer Aβ neurotoxicity: Promotion by antichymotrypsin, ApoE4; inhibition by Aβ-related peptides

Two inflammation-associated proteins found in the Alzheimer amyloid deposits—α1-antichymotrypsin (ACT) and apolipoprotein E4 (apoE4)—have been shown to be genetic risk factors for the development of Alzheimerʹs disease and to promote the polymerization of the Aβ peptide into amyloid filaments in vitro. In the present study, we show that ACT and apoE4 increase the neurotoxicity of the Aβ peptide in parallel with their promotion of filament formation. Preincubation of ACT or apoE4 with small Aβ-related peptides, or of apoE4 with apoE2, abrogated their subsequent ability to promote both the formation and the neurotoxicity of Aβ filaments. These results indicate that ACT and apoE4 may play a stimulatory role in the formation of neurotoxic amyloid in Alzheimerʹs disease, and that their amyloid promoting activity can be blocked by inhibitory peptides.