title: An Alzheimer's disease-specific beta-amyloid fragment signature in cerebrospinal fluid.
abstract: Pathogenic events in Alzheimer's disease (AD) involve an imbalance between the production and clearance of the neurotoxic beta-amyloid peptide (Abeta), especially the 42 amino acid peptide Abeta1-42. While much is known about the production of Abeta1-42, many questions remain about how the peptide is degraded. To investigate the degradation pattern, we developed a method based on immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry that determines the Abeta degradation fragment pattern in cerebrospinal fluid (CSF). We found in total 18 C-terminally and 2 N-terminally truncated Abeta peptides and preliminary data indicated that there were differences in the detected Abeta relative abundance pattern between AD and healthy controls. Here, we provide direct evidence that an Abeta fragment signature consisting of Abeta1-16, Abeta1-33, Abeta1-39, and Abeta1-42 in CSF distinguishes sporadic AD patients from non-demented controls with an overall accuracy of 86%.
authors.affiliation: Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, University of Göteborg, Sahlgrenska University Hospital, Mölndal, Sweden. erik.portelius@neuro.gu.se
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brinkmalm
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Ann
authors.initials: A
authors.lastname: Westman-Brinkmalm
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments