title: The amyloid-β degradation pattern in plasma--a possible tool for clinical trials in Alzheimer's disease.
abstract: Amyloid beta (Aβ) is the main component of plaques, the central neuropathological hallmark in Alzheimer's disease (AD). Aβ is derived from the amyloid precursor protein (APP) by β- and γ-secretase-mediated cleavages. A large number of Aβ peptides are found in cerebrospinal fluid and these peptides are produced in specific metabolic pathways, which are important for diagnosis, in drug development and to explore disease pathogenesis. To investigate whether a similar pattern could be found also in blood samples, an immunoprecipitation (IP) based method for enrichment of Aβ peptides from human plasma was developed. The peptides were analyzed using matrix-assisted-laser-desorption/ionization time-of-flight/time-of-flight mass spectrometry for Aβ profiling and selected reaction monitoring (SRM) for MS quantification of Aβ1-38, Aβ1-40 and Aβ1-42 using tripe quadrupole MS. Sixteen N- or C-terminally truncated Aβ peptides were reproducibly detected in human plasma, of which 11 were verified by tandem MS. In a pilot study including 9 AD patients and 10 controls, where Aβ1-38, Aβ1-40 and Aβ1-42 were quantified using SRM, no AD-associated change in plasma levels of the peptides were observed. Using MS-based measurement techniques, we show that several Aβ peptides can be monitored in a single analysis and the developed methods have the potential to be used as a read out in clinical trials of drugs affecting APP processing or Aβ homeostasis.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Josef
authors.initials: J
authors.lastname: Pannee
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Törnqvist
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anni
authors.initials: A
authors.lastname: Westerlund
authors.affiliation: Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.affiliation: Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brinkmalm
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Rita
authors.initials: R
authors.lastname: Persson
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.affiliation: Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Department of Endocrinology, Skaraborg Central Hospital, SE-541 85 Skövde, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Department of Neuropsychiatry, Skaraborg Central Hospital, SE-521 85 Falköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Johansson
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, England.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: erik.portelius@neuro.gu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid beta; Immunoprecipitation; Mass spectrometry; Plasma