The inflammation-sensitive protein alpha 1-anti-chymotrypsin neutralizes fibrillar aggregation and cytotoxicity of the beta-amyloid peptide more effectively than alpha 1-antitrypsin

objectives: A neuroinflammatory process, triggered by amyloid-beta (A beta)-peptide, is thought to play a central role in the neurodegencrative process leading to Alzheimer's disease (AD). A beta(25-35) retains the functionality of A beta(42) and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) alpha l-antichyinotrypsin (AlACT) and alpha l-antitrypsin (AlAT) on fibrillar aggregation and cytotoxicity. Design and methods: Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of A[ cytotoxicity. For studies of A beta-fibrillar aggregation CSF levels of AlACT (0.041 mu M)/AlAT (0. 11 mu M) were incubated with Congo Red dye 25 mu M+ A beta(25-35) 10 mu M noting the formation of visible aggregates and spectrophotometrie changes over 24 h. Results: A I ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A] AT at CSF reported levels failed to cause a similar inhibition. Conclusions: A1ACT neutralizes fibrillar aggregation and cytotoxicity of A beta-peptide more effectively than A1AT. Both proteins are known to be co-deposited with A beta within senile plaques of AD brains. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.