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 (Aβ)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimerʹs disease (AD). Aβ25–35 retains the functionality of Aβ42 and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) α1-antichymotrypsin (A1ACT) and α1-antitrypsin (A1AT) 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 Aβ-cytotoxicity. For studies of Aβ-fibrillar aggregation CSF levels of A1ACT (0.041 μM)/A1AT (0.11 μM) were incubated with Congo Red dye 25 μM + Aβ25–35 10 μM noting the formation of visible aggregates and spectrophotometric changes over 24 h. Results: A1ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported levels failed to cause a similar inhibition. Conclusions: A1ACT neutralizes fibrillar aggregation and cytotoxicity of Aβ-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Aβ within senile plaques of AD brains.