title: Identification of peptide products from enzymatic degradation of amyloid beta.
abstract: Deposition of insoluble amyloid plaques is one of the known hallmarks of Alzheimer's disease. Amyloid beta 1-42 is the main component in these plaques, and the soluble oligomers of this peptide are believed to contribute to synaptic degradation and dementia. Enzymatic hydrolysis of amyloid beta is important to keep its tissue concentration low to avoid oligomerization. We have employed four enzymes involved in in vivo degradation of amyloid beta, to identify amyloid beta 1-42 hydrolysis products in vitro. Liquid chromatography coupled to (high resolution) mass spectrometry was used to identify the proteolysis products. Novel cleavage sites were discovered for all four enzymes. For each enzyme, the peptide was incubated for several different periods from 0.5 to 210 min, and the proteolysis products from each period were characterized. Thus, both the initial cleavage sites and the full degradation profiles were revealed. Knowledge about the fate of amyloid beta is important to better understand the mechanism underlying Alzheimer's disease, and the reported proteolysis products can be used as targets in future investigations on amyloid beta clearance.
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital, University of Oslo, Norway. Electronic address: magnus.rogeberg@ahus.no.
authors.forename: Magnus
authors.initials: M
authors.lastname: Rogeberg
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital, University of Oslo, Norway.
authors.forename: Camilla B
authors.initials: CB
authors.lastname: Furlund
authors.affiliation: Unit of Medical Biochemistry, Division of Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Morten K
authors.initials: MK
authors.lastname: Moe
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D006801:Humans; D006868:Hydrolysis; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D059748:Proteolysis
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments
keywords: Alzheimer's disease; Amyloid beta; Enzymatic degradation; Liquid chromatography mass spectrometry