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Neurobiol Aging. 2015 Jul;36(7):2241-2247. doi: 10.1016/j.neurobiolaging.2015.03.011. Epub 2015 Mar 25.

Endogenous murine Aβ increases amyloid deposition in APP23 but not in APPPS1 transgenic mice.

Author information

1
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany; Graduate School for Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, Germany.
2
Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
3
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
4
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
5
Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
6
Department of Psychiatry, New York University School of Medicine, New York, NY, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
7
Department of Chemistry, IFM, Linköping University, Linköping, Sweden.
8
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. Electronic address: mathias.jucker@uni-tuebingen.de.
9
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. Electronic address: bettina.braun@uni-tuebingen.de.

Abstract

Endogenous murine amyloid-β peptide (Aβ) is expressed in most Aβ precursor protein (APP) transgenic mouse models of Alzheimer's disease but its contribution to β-amyloidosis remains unclear. We demonstrate ∼ 35% increased cerebral Aβ load in APP23 transgenic mice compared with age-matched APP23 mice on an App-null background. No such difference was found for the much faster Aβ-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine Aβ, and immunoelectron microscopy revealed a tight association of murine Aβ with human Aβ fibrils. Deposition of murine Aβ was considerably less efficient compared with the deposition of human Aβ indicating a lower amyloidogenic potential of murine Aβ in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human Aβ and deposits of mixed human-murine Aβ. Our data demonstrate a differential effect of murine Aβ on human Aβ deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse Aβ may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.

KEYWORDS:

APP transgenic mouse models; Alzheimer's disease; Beta-amyloid; Mixed amyloid-beta (Aβ) fibrils; Murine APP knockout; Murine amyloid-beta (Aβ)

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