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Modeling familial British and Danish dementia

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Abstract

Familial British dementia (FBD) and familial Danish dementia (FDD) are two autosomal dominant neurodegenerative diseases caused by mutations in the BRI 2 gene. FBD and FDD are characterized by widespread cerebral amyloid angiopathy (CAA), parenchymal amyloid deposition, and neurofibrillary tangles. Transgenic mice expressing wild-type and mutant forms of the BRI2 protein, Bri 2 knock-in mutant mice, and Bri 2 gene knock-out mice have been developed. Transgenic mice expressing a human FDD-mutated form of the BRI 2 gene have partially reproduced the neuropathological lesions observed in FDD. These mice develop extensive CAA, parenchymal amyloid deposition, and neuroinflammation in the central nervous system. These animal models allow the study of the molecular mechanism(s) underlying the neuronal dysfunction in these diseases and allow the development of potential therapeutic approaches for these and related neurodegenerative conditions. In this review, a comprehensive account of the advances in the development of animal models for FBD and FDD and of their relevance to the study of Alzheimer disease is presented.

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Acknowledgments

The authors are grateful to Debra Lucas, Janice Pennington, and Rose Richardson for their technical assistance. This study was supported by grants from the National Institute of Health NS050227, AG10133, AG027139, and AG033007, by the Alzheimer’s Association (IIRG-05-14220), and by the American Health Assistance Foundation (A2008-304).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Indiana Alzheimer Disease Center, Indiana University School of Medicine, 635 Barnhill Drive MSB A136, Indianapolis, IN, 46202, USA

    Holly J. Garringer, Jill Murrell, Bernardino Ghetti & Ruben Vidal

  2. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Luciano D’Adamio

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  1. Holly J. Garringer
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  2. Jill Murrell
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  3. Luciano D’Adamio
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  4. Bernardino Ghetti
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  5. Ruben Vidal
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Correspondence to Ruben Vidal.

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Garringer, H.J., Murrell, J., D’Adamio, L. et al. Modeling familial British and Danish dementia. Brain Struct Funct 214, 235–244 (2010). https://doi.org/10.1007/s00429-009-0221-9

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