Alpha 1-antichymotrypsin interaction with A beta (1-42) does not inhibit fibril formation but attenuates the peptide toxicity.

alpha 1-Antichymotrypsin (ACT) is intimately associated with senile plaques in the Alzheimer's diseased (AD) brain. It was reported that ACT can promote the polimerization of A beta (1-42) into amyloid filaments. It was suggested that neurotoxic amyloid deposits arise when beta-peptide is induced to form fibrils by ACT or other amyloid-promoting factors (pathological chaperones) expressed in AD brain. However, it was reported recently that ACT can inhibit fibrillization of A beta (1-40) and disaggregate pre-formed beta-amyloid fibrils of this synthetic A beta peptide. Our previous study [Aksenova et al., Neurosci. Lett., 411 (1996) 43-48] confirmed that ACT is able to inhibit A beta (1-40) aggregation into fibrils, but it was shown that at the same time ACT does not change the peptide cytotoxicity. In this report we have observed that interaction of ACT with A beta (1-42), unlike that for ACT-A beta (1-40) interaction, does not prevent the formation of insoluble A beta (1-42) aggregates, but completely blocks the peptide's toxicity in rat hippocampal cell cultures. These results are discussed in terms of the potential double role of peptide-protein interactions on A beta aggregation and neurotoxicity.