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  • Review Article
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Rodent models for Alzheimer disease

Abstract

Animal models are indispensable tools for Alzheimer disease (AD) research. Over the course of more than two decades, an increasing number of complementary rodent models has been generated. These models have facilitated testing hypotheses about the aetiology and progression of AD, dissecting the associated pathomechanisms and validating therapeutic interventions, thereby providing guidance for the design of human clinical trials. However, the lack of success in translating rodent data into therapeutic outcomes may challenge the validity of the current models. This Review critically evaluates the genetic and non-genetic strategies used in AD modelling, discussing their strengths and limitations, as well as new opportunities for the development of better models for the disease.

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Fig. 1: Alignment of human and mouse forms of three key proteins implicated in Alzheimer disease.
Fig. 2: Structural differences between the three key molecules implicated in Alzheimer disease.
Fig. 3: Principal approaches in generating rodent models.

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Acknowledgements

J.G. and L.-G.B. acknowledge support by the National Health and Medical Research Council of Australia (grants GNT1127999 and GNT1147569). M.G. is an Honorary Professor in the Department of Clinical Neurosciences of the University of Cambridge. This work was supported by the UK Medical Research Council (grant MC_U105184291). L.-G.B. is supported by the Peter Hilton Fellowship. The authors thank R. Tweedale for critically reading the manuscript.

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Nature Reviews Neuroscience thanks E. Roberson, J. Shen and T. Wisniewski for their contribution to the peer review of this work.

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Correspondence to Jürgen Götz.

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Alzforum: https://www.alzforum.org/research-models/alzheimers-disease

Collaborative Cross (CC): https://www.jax.org/news-and-insights/2009/april/the-collaborative-cross-a-powerful-systems-genetics-tool

International Mouse Phenotyping Consortium: http://www.mousephenotype.org/

MODEL-AD Centers: https://www.jax.org/research-and-faculty/research-centers/alzheimers-disease-center/alzheimers-disease-precision-models-center

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Glossary

Amyloid-β cascade hypothesis

Hypothesis postulating that the neurodegeneration in AD is caused by the abnormal accumulation of Aβ, which subsequently leads to tau pathology and neuronal loss.

Tau seeding

Pathological forms of tau that transfer their properties in a process of templating to non-aggregated forms of tau.

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Götz, J., Bodea, LG. & Goedert, M. Rodent models for Alzheimer disease. Nat Rev Neurosci 19, 583–598 (2018). https://doi.org/10.1038/s41583-018-0054-8

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