title: A protease activity associated with acetylcholinesterase releases the membrane-bound form of the amyloid protein precursor of Alzheimer's disease.
abstract: Amyloid deposits in the brains of patients with Alzheimer's disease (AD) contain a protein (beta A4) which is abnormally cleaved from a larger transmembrane precursor protein (APP). APP is believed to be normally released from membranes by the action of a protease referred to as APP secretase. Amyloid deposits have also been shown to contain the enzyme acetylcholinesterase (AChE). In this study, a protease activity associated with AChE was found to possess APP secretase activity, stimulating the release of a soluble 100K form of APP from HeLa cells transfected with an APP cDNA. The AChE-associated protease was strongly and specifically inhibited by soluble APP (10 nM) isolated from human brain. The AChE-associated protease cleaved a synthetic beta A4 peptide at the predicted cleavage site. As AChE is decreased in AD, a deficiency of its associated protease might explain why APP is abnormally processed in AD.
authors.affiliation: Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: D H
authors.initials: DH
authors.lastname: Small
authors.forename: R D
authors.initials: RD
authors.lastname: Moir
authors.forename: S J
authors.initials: SJ
authors.lastname: Fuller
authors.forename: S
authors.initials: S
authors.lastname: Michaelson
authors.forename: A I
authors.initials: AI
authors.lastname: Bush
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Milward
authors.forename: C
authors.initials: C
authors.lastname: Hilbich
authors.forename: A
authors.initials: A
authors.lastname: Weidemann
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism* / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002462:Cell Membrane / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D011480:Protease Inhibitors; D007611:Aprotinin; D000110:Acetylcholinesterase; D010450:Endopeptidases