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Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy

Molecular Psychiatry volume 9, pages 664–683 (2004)Cite this article

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as β-amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. β-Amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In β-amyloid-producing transgenic mice, memory impairment was associated with increased levels of β-amyloid. Active and passive β-amyloid-directed immunization caused the removal of β-amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.

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Acknowledgements

We thank Jay Tracy for critical reading of the manuscript. This work was supported by grants from the A+D Fonds of the Swiss Academy of Medical Sciences (SAMS), the Olga Mayenfisch Foundation, the Kurt und Senta Herrmann Foundation, and the Swiss National Science Foundation to JG.

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  1. Division of Psychiatry Research, University of Zürich, Zürich, Switzerland

    J Götz, J R Streffer, D David, A Schild, F Hoerndli, L Pennanen, P Kurosinski & F Chen

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Götz, J., Streffer, J., David, D. et al. Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy. Mol Psychiatry 9, 664–683 (2004). https://doi.org/10.1038/sj.mp.4001508

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