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Modeling familial Danish dementia in mice supports the concept of the amyloid hypothesis of Alzheimer's disease

Coomaraswamy, Janaky and Kilger, Ellen and Wölfing, Heidrun and Schäfer, Claudia and Kaeser, Stephan and Wegenast-Braun, Bettina and Hefendehl, Jasmin K and Wolburg, Hartwig and Mazella, Matthew and Ghiso, Jorge and Goedert, Michel and Akiyama, Haruhiko and Garcia-Sierra, Francisco and Wolfer, David and Mathews, Paul M and Jucker, Mathias (2010) Modeling familial Danish dementia in mice supports the concept of the amyloid hypothesis of Alzheimer's disease. Proceedings of the National Academy of Science USA, 107 (17). pp. 7969-7974.

Abstract

Familial Danish Dementia (FDD) is a progressive neurodegenerative disease with cerebral deposition of Dan-amyloid (ADan), neuroinflammation, and neurofibrillary
tangles - hallmark characteristics remarkably similar to those in Alzheimer´s disease (AD). We have generated transgenic (tg) mouse models of FDD that exhibit the age-dependent deposition of ADan throughout the brain with associated amyloid angiopathy, microhemorrhage, neuritic dystrophy, and neuroinflammation. Tg mice are impaired in the Morris water maze and exhibit increased anxiety in the open field. When crossed with TauP301S tg mice, ADan accumulation induces neurofibrillary lesions, in all aspects similar to the Tau
lesions observed in crosses between β-amyloid (Aβ) depositing mice and TauP301S mice. While these observations argue for shared mechanisms of downstream pathophysiology for the sequence-unrelated ADan and Aβ peptides, the lack of co-deposition of the two peptides in crosses between ADan- and Aβ-depositing mice points also to distinguishing properties of the peptides. Our results support the concept of the amyloid hypothesis for AD and related dementia and suggest that different proteins prone to amyloid formation can drive strikingly similar pathogenic pathways in the brain.

Item Type: Article
Keywords: ADan; ABeta; tau; neurodegeneration; mouse model
Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2734

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