1. Endogenous murine Aβ increases amyloid deposition in APP23 but not in APPPS1 transgenic mice.
- Author
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Mahler J, Morales-Corraliza J, Stolz J, Skodras A, Radde R, Duma CC, Eisele YS, Mazzella MJ, Wong H, Klunk WE, Nilsson KPR, Staufenbiel M, Mathews PM, Jucker M, and Wegenast-Braun BM
- Subjects
- Animals, Disease Models, Animal, Humans, Mice, Transgenic, Alzheimer Disease genetics, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Amyloid beta-Protein Precursor genetics, Brain metabolism
- 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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