ENHANCED AGGREGATION OF BETA-AMYLOID-CONTAINING PEPTIDES BY EXTRACELLULAR-MATRIX AND THEIR DEGRADATION BY THE 68 KDA SERINE-PROTEASE PREPARED FROM HUMAN BRAIN

To explore whether extracellular matrix components in human brain affe ct the deposition and aggregation of beta-amyloid containing peptides, human brain samples from patients with sporadic Alzheimer's disease a nd normal aged were analyzed by Western blot analysis. All major beta- amyloid-containing peptides contained epitope(s) which is recognized b y anti heparan sulfate antibody. Incubation of brain beta-amyloid-cont aining peptides with human collagen type IV in neutral pH efficiently generated a high molecular weight aggregated band, approximately 5-fol d that of the control sample. We have previously found a serine protea se which is capable of cleaving an oligopeptide at the N-terminus of b eta-amyloid. In this study, the protease, which also contains heparan sulfate glycoconjugates, degraded the above brain peptides as natural substrates, although with different efficiency, These findings suggest that extracellular matrix components affect the processing and aggreg ation of beta-amyloid-containing peptides in human brain. (C) 1996 Els evier Science Ireland Ltd.