title: Differential transgene expression patterns in Alzheimer mouse models revealed by novel human amyloid precursor protein-specific antibodies.
abstract: Alzheimer's disease (AD) is histopathologically characterized by neurodegeneration, the formation of intracellular neurofibrillary tangles and extracellular Aβ deposits that derive from proteolytic processing of the amyloid precursor protein (APP). As rodents do not normally develop Aβ pathology, various transgenic animal models of AD were designed to overexpress human APP with mutations favouring its amyloidogenic processing. However, these mouse models display tremendous differences in the spatial and temporal appearance of Aβ deposits, synaptic dysfunction, neurodegeneration and the manifestation of learning deficits which may be caused by age-related and brain region-specific differences in APP transgene levels. Consequentially, a comparative temporal and regional analysis of the pathological effects of Aβ in mouse brains is difficult complicating the validation of therapeutic AD treatment strategies in different mouse models. To date, no antibodies are available that properly discriminate endogenous rodent and transgenic human APP in brains of APP-transgenic animals. Here, we developed and characterized rat monoclonal antibodies by immunohistochemistry and Western blot that detect human but not murine APP in brains of three APP-transgenic mouse and one APP-transgenic rat model. We observed remarkable differences in expression levels and brain region-specific expression of human APP among the investigated transgenic mouse lines. This may explain the differences between APP-transgenic models mentioned above. Furthermore, we provide compelling evidence that our new antibodies specifically detect endogenous human APP in immunocytochemistry, FACS and immunoprecipitation. Hence, we propose these antibodies as standard tool for monitoring expression of endogenous or transfected APP in human cells and APP expression in transgenic animals.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Höfling
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zeitschel
authors.affiliation: Department of Neuroscience, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Moschke
authors.affiliation: Institute for Advanced Study, Technische Universität München, Garching, Germany.|Institut für Pathologie und Pathologische Anatomie, Technische Universität München, Munich, Germany.
authors.forename: Alperen
authors.initials: A
authors.lastname: Serdaroglu
authors.affiliation: Department of Experimental Therapy, Präklinisches Experimentelles Tierzentrum (PETZ), Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Fabio
authors.initials: F
authors.lastname: Canneva
authors.affiliation: Department of Experimental Therapy, Präklinisches Experimentelles Tierzentrum (PETZ), Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.affiliation: Department of Neuroscience, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: De Simoni
authors.affiliation: Department of Neuroscience, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Jäger
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Molecular Immunology, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Roßner
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Institute for Advanced Study, Technische Universität München, Garching, Germany.|Neuroproteomics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Lichtenthaler
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Institute for Advanced Study, Technische Universität München, Garching, Germany.|Institut für Pathologie und Pathologische Anatomie, Technische Universität München, Munich, Germany.|Neuroproteomics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Peer-Hendrik
authors.initials: PH
authors.lastname: Kuhn
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D015203:Reproducibility of Results; D019076:Transgenes / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; D000906:Antibodies
keywords: Alzheimer's disease; amyloid precursor protein; immunohistochemistry; monoclonal antibody; neuropathology; transgenic animal models