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Animal Models of Dementia pp 371–385Cite as

APP-Based Transgenic Models: The PDAPP Model

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Part of the book series: Neuromethods ((NM,volume 48))

Abstract

The PDAPP mouse has been a very useful model for studying mechanisms underlying amyloid-β (Aβ) metabolism, aggregation, and deposition, and for aiding in the development of new diagnostic and therapeutic approaches for Alzheimer’s disease (AD). One of the initial difficulties in producing a mouse model that was useful to study AD was creating an easily manipulated small animal model that demonstrated some of the key in vivo neuropathological hallmarks of the disease. The PDAPP model was the first transgenic mouse to overexpress the human amyloid precursor protein (hAPP) that successfully recapitulated several neuropathological features characteristic of AD. These include Aβ deposition in both diffuse and neuritic plaques, cerebral amyloid angiopathy, astrocytosis, microgliosis, hippocampal atrophy, synaptic alterations, and behavioral deficits. Many of the histological, biochemical, and structural alterations present in the PDAPP mouse closely resemble the changes found in the brain of AD patients, especially the temporal and spatial-specific deposition of Aβ in the brain. The animals, however, did not develop tauopathy or significant neuronal cell death. Because of these properties, the PDAPP mouse has proven to be an attractive model to study the disease process underlying aspects of AD that are related to Aβ aggregation and its consequences. The PDAPP mouse has been extensively used to study the effect of genetic factors that modify AD, as well as Aβ-binding proteins and their effect on Aβ deposition. It has also been widely used to characterize the potential use of active and passive immunization in both the diagnosis and treatment of AD.

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Acknowledgments

This work was supported by NIH grants AG13956 and P01-NS32636.

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Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, St. Louis, MO, Washington, USA

    Jacob M. Basak & David M. Holtzman

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  1. Jacob M. Basak
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  2. David M. Holtzman
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Editors and Affiliations

  1. Institute Born-Bunge, Lab of Neurochemistry & Behaviour, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium

    Peter Paul De Deyn

  2. Institute Born-Bunge, Lab of Neurochemistry & Behaviour, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium

    Debby Van Dam

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Basak, J.M., Holtzman, D.M. (2011). APP-Based Transgenic Models: The PDAPP Model. In: De Deyn, P., Van Dam, D. (eds) Animal Models of Dementia. Neuromethods, vol 48. Humana Press. https://doi.org/10.1007/978-1-60761-898-0_18

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  • DOI: https://doi.org/10.1007/978-1-60761-898-0_18

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