Amyloid and tau deposition in the brain of a transgenic mouse model for familial Danish dementia

Ruben Vidal, PhD
Indiana University School of Medicine (Indianapolis, IN)
Year Awarded:
2008
Grant Duration:
April 1, 2008 to March 31, 2010
Disease:
Alzheimer's Disease
Award Amount:
$100,000
Grant Reference ID:
A2008304
Award Type:
Pilot
Award Region:
US Midwestern
Ruben Vidal, PhD

Double transgenic model of familial Danish dementia with plaques and tangles

Summary

Familial Danish Dementia (FDD) is similar clinically and pathologically to AD. The aim of this pilot proposal is to develop a double transgenic animal model of FD. These mice will be used to study the deposition of the Danish amyloid peptide and tau and compare these to similar processes in Alzheimer's disease.

Details


Alzheimer disease (AD) afflicts more than 4 million Americans at a cost to the economy in excess of $100 billion. The psychological and emotional burden to patients and care-givers is incalculable. Given the absence of disease-modifying therapeutics and accurate diagnostics, there is a need to better comprehend AD's pathogenic mechanism. We have developed an animal model for a similar neurodegenerative disease named familial Danish dementia (FDD). FDD shares many clinical and pathological similarities with AD, including deposition of amyloid (only different from the one found in AD in primary sequence) and neurofibrillary tangle formation (similar to the one found in AD). We will perform biochemical, neuropathological and behavioral studies in an animal model that should provide the basis for the identification of the cascade of events that lead to FDD. We believe that the study of this model may provide insights into the role of amyloid and neurofibrillary tangle not only in FDD but also in AD.

Publications

Garringer HJ, Murrell J, D'Adamio L, Ghetti B, Vidal R. (2010) Modeling familial British and Danish dementia. Brain Struct Funct. 214(2-3):235-44. Epub 2009 Sep 25.  

This study reports a comprehensive review of the current animal models for familial British and Danish dementia, including the first double FDD and tau transgenic mouse model. Giliberto L, Matsuda S, Vidal R, D'Adamio L. Generation and initial characterization of FDD knock in mice. PLoS One. 2009 Nov 18;4(11):e7900.  

This study reports the first knock-in model for FDD. Vidal, R. Mouse models of British and Danish dementia. Symposium. Related Dementias. ICAD 2010. Alzheimer's &Dementia: the Journal of the Alzheimer's Association [conference abstract] In this presentation, we will review current animal models for familial British and Danish dementia, including our double FDD and tau transgenic mouse model.
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