title: A calcium-activated protease from Alzheimer's disease brain cleaves at the N-terminus of the amyloid beta-protein.
abstract: Alzheimer's disease, Down's syndrome, and to a far lesser extent, normal aged brains exhibit abnormal extracellular deposits of amyloid. The major component of brain amyloid is the beta-protein, a 4Kd fragment of the larger beta-protein precursor. The finding of the abnormally processed beta-protein and a protease inhibitor (alpha 1-antichymotrypsin) in the amyloid deposits prompted us to search for proteases which may generate the beta-protein from its precursor. We now report on the presence and partial purification of one such proteolytic activity from Alzheimer's brain. Normal physiologic C-terminal cleavage of the secreted form of the beta-protein precursor occurs in the middle of the beta-protein suggesting that the beta-protein accumulates due to an alternative degradation pathway. We propose here that the protease activity we describe participates in this abnormal pathway.
authors.affiliation: Arthritis Center, Boston University School of Medicine, MA 02118.
authors.forename: C R
authors.initials: CR
authors.lastname: Abraham
authors.forename: J
authors.initials: J
authors.lastname: Driscoll
authors.forename: H
authors.initials: H
authors.lastname: Potter
authors.forename: W E
authors.initials: WE
authors.lastname: Van Nostrand
authors.forename: P
authors.initials: P
authors.lastname: Tempst
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D002848:Chromatography, DEAE-Cellulose; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D016229:Amyloid beta-Peptides; D012697:Serine Endopeptidases; D002118:Calcium