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Hodges, John R

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Frontotemporal Dementias: Genotypes and Phenotypes

Lee, Virginia M-Y

15 March 2000 - 29 February 2016
NATIONAL INSTITUTE ON AGING
Total Funding: $ 19,741,888

FY 2012
5P01AG017586-12
$ 1,932,056
FY 2011
2P01AG017586-11
$ 1,962,143
FY 2009
5P01AG017586-10
$ 1,960,885
FY 2010
3P01AG017586-10S1
$ 158,451
FY 2008
5P01AG017586-09
$ 1,914,300
FY 2007
5P01AG017586-08
$ 1,909,789
FY 2006
3P01AG017586-07S1
$ 276,519
FY 2006
5P01AG017586-07
$ 1,613,272
FY 2005
2P01AG017586-06
$ 1,600,093
FY 2004
5P01AG017586-05
$ 1,292,648
FY 2003
5P01AG017586-04
$ 1,327,540
FY 2002
5P01AG017586-03
$ 1,304,515
FY 2001
3P01AG017586-02S1
$ 37,452
FY 2001
3P01AG017586-02S2
$ 50,000
FY 2001
5P01AG017586-02
$ 1,225,672
FY 2000
1P01AG017586-01
$ 1,176,553
 
 
$ 19,741,888
Abstract

DESCRIPTION (provided by applicant): The competing renewal of this Program Project Grant (PPG) builds on tremendous progress made by PPG investigators during the last funding cycle in defining the genotypes and phenotypes of frontotemporal lobar degeneration (FTLD). Collectively, our work has substantively redefined the neuropathology of FTLD as those with tau tangles (FTLD-Tau) and those with TDP-43 inclusions (FTLD-TDP). Moreover, genome-wide association (GWAS) studies led by PPG investigators on autopsy-confirmed FTLD-TDP as well as on autopsy-confirmed progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD), subtypes of FTLD-Tau, identified additional genetic risk factors and modifiers for FTLD-TDP and FTLD-Tau, respectively. During the next funding period, PPG investigators will exploit these accomplishments by proposing a set of bold new objectives for FTLD research that will be implemented through 5 Cores and 4 Projects. Specifically, they will define clinical phenotypes of FTLD subtypes and determine if they predict cases with FTLD-Tau or FTLD-TDP, identify new FTLD mutations and conduct additional genetic studies to identify genes that modify tau pathogenicity, determine the mechanisms of tau tangle formation and evaluate genes and proteins that modify TDP-43 pathogenicity through cell culture, C. elegans and transgenic mouse models. The proposed studies will provide important insights into mechanisms of FTLD and the diagnosis and treatment of these disorders.

266 Resulting Publications

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