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Guinea Pigs as a Nontransgenic Model for APP Processing in Vitro and in Vivo

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Abstract

Alzheimer's disease (AD) is characterized, amongst others, by the appearance of vascular and parenchymal β-amyloid deposits in brain. Such aggregates are mainly composed of β-amyloid peptides, which are derived by proteolytic processing of a larger amyloid precursor protein (APP). APP is highly conserved among mammalian species, but experimental studies in rodents are often hampered by the humble APP-processing in the amyloidogenic pathway and by the inability of rodent β-amyloid peptides to form higher molecular aggregates such as soluble oligomers and insoluble β-amyloid plaques. Thus, there is need for in vitro and in vivo model systems that allow identification of factors that increase amyloidogenic APP processing and accelerate β-amyloid plaque formation and testing the potency of pharmacological manipulations to ameliorate β-amyloid load in brain. Transgenic mice that overexpress human APP containing AD-associated mutations that favor the amyloidogenic pathway of APP processing represent such a model. However, mutations of the APP gene are not frequent in AD and, therefore, the mechanisms of β-amyloid plaque formation, the composition of β-amyloid plaques, and the accompanying tissue response in brain of these animals may be different from that in AD. In contrast, guinea pigs express β-amyloid peptides of the human sequence and appear to represent a more physiological model to examine the long-term effects of experimental manipulations on APP processing and β-amyloid plaque formation in vivo. Additionally, APP processing in guinea pig primary neuronal cultures has been shown to be similar to cultures of human origin. In this article we highlight the advantages and limitations of using guinea pigs as experimental models to study APP processing.

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  1. Mike Beck

    Present address: Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307, Dresden, Germany

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  1. Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany

    Mike Beck, Volker Bigl & Steffen Roßner

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Beck, M., Bigl, V. & Roßner, S. Guinea Pigs as a Nontransgenic Model for APP Processing in Vitro and in Vivo . Neurochem Res 28, 637–644 (2003). https://doi.org/10.1023/A:1022850113083

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