PROSTAGLANDIN-E2 INDUCED POLYMERIZATION OF HUMAN ALPHA-1-ANTICHYMOTRYPSIN AND SUPPRESSED ITS PROTEASE INHIBITORY ACTIVITY - IMPLICATIONS FOR ALZHEIMERS-DISEASE

Different molecular forms of a-l-antichymotrypsin (ACT) in sera and ce rebrospinal fluids fi om patients with Alzheimer's disease (AD) were d etected. Monomeric and polymeric ACT were observed by polyacrylamide g el electrophoresis of both sera and cerebrospinal fluids. ACT polymers were increased in AD patients with the apolipoprotein E (APOE) 4 alle le. Increased levels of inactive ACT molecules were also detected in b rain homogenates of patients with the APOE 4 allele. Experimental cond itions promoting in vitro polymerization of ACT and the effect of poly merization on the biological activity of this serpin were also explore d. Incubation of this serpin with prostaglandin of E series (PGE 2) in duced ACT polymerization and decreased its activity. Amyloid beta-pept ide(1-42) did not significantly affected the biological activity of AC T. Inactivation of protease inhibitors by inflammatory molecules such as PGE 2 released fi om activated microglia in AD brains may promote a myloid deposition and neurodegeneration. (C) 1998 Academic Press.