APP mouse models for Alzheimer's disease preclinical studies |
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| Authors: | Hiroki Sasaguri Per Nilsson Shoko Hashimoto Kenichi Nagata Takashi Saito Bart De Strooper John Hardy Robert Vassar Bengt Winblad Takaomi C Saido |
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| Affiliation: | 1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Japan;2. Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan;3. Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden;4. Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;5. Dementia Research Institute, University College London, London, UK;6. Department for Neurosciences, KU Leuven, Leuven, Belgium;7. VIB Center for Brain and Disease Research, Leuven, Belgium;8. Reta Lila Research Laboratories and the Department of Molecular Neuroscience, University College London Institute of Neurology, London, UK;9. Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA |
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| Abstract: | Animal models of human diseases that accurately recapitulate clinical pathology are indispensable for understanding molecular mechanisms and advancing preclinical studies. The Alzheimer's disease (AD) research community has historically used first‐generation transgenic (Tg) mouse models that overexpress proteins linked to familial AD (FAD), mutant amyloid precursor protein (APP), or APP and presenilin (PS). These mice exhibit AD pathology, but the overexpression paradigm may cause additional phenotypes unrelated to AD. Second‐generation mouse models contain humanized sequences and clinical mutations in the endogenous mouse App gene. These mice show Aβ accumulation without phenotypes related to overexpression but are not yet a clinical recapitulation of human AD. In this review, we evaluate different APP mouse models of AD, and review recent studies using the second‐generation mice. We advise AD researchers to consider the comparative strengths and limitations of each model against the scientific and therapeutic goal of a prospective preclinical study. |
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| Keywords: | Alzheimer's disease amyloid precursor protein amyloid β peptide App knock‐in APP transgenic |
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