title: Beta-amyloid peptide variants in brains and cerebrospinal fluid from amyloid precursor protein (APP) transgenic mice: comparison with human Alzheimer amyloid.
abstract: In this study, we report a detailed analysis of the different variants of amyloid-β (Aβ) peptides in the brains and the cerebrospinal fluid from APP23 transgenic mice, expressing amyloid precursor protein with the Swedish familial Alzheimer disease mutation, at different ages. Using one- and two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry, we identified the Aβ peptides Aβ(1-40), -(1-42), -(1-39), -(1-38), -(1-37), -(2-40), and -(3-40) as well as minor amounts of pyroglutamate-modified Aβ (Aβ(N3pE)) and endogenous murine Aβ in brains from 24-month-old mice. Chemical modifications of the N-terminal amino group of Aβ were identified that had clearly been introduced during standard experimental procedures. To address this issue, we additionally applied amyloid extraction in ultrapure water. Clear differences between APP23 mice and Alzheimer disease (AD) brain samples were observed in terms of the relative abundance of specific variants of Aβ peptides, such as Aβ(N3pE), Aβ(1-42), and N-terminally truncated Aβ(2/3-42). These differences to human AD amyloid were also noticed in a related mouse line transgenic for human wild type amyloid precursor protein. Taken together, our findings suggest different underlying molecular mechanisms driving the amyloid deposition in transgenic mice and AD patients.
authors.affiliation: Department of Psychiatry and Psychotherapy, LVR-Klinikum, Essen, University of Duisburg-Essen, D-45147 Essen, Germany.
authors.forename: Heinke
authors.initials: H
authors.lastname: Schieb
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kratzin
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.forename: Sabine
authors.initials: S
authors.lastname: Rabe
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Hans W
authors.initials: HW
authors.lastname: Klafki
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013045:Species Specificity
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor